Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine

*Andrés J. Ursa Herguedas*

## **Abstract**

Non-pharmacological interventions (NI) have been known since before modern pharmacology was developed. They occupy a prominent place in the healthcare sciences. The aim of this chapter is to show the role of NPI in medicine today. The reasons for implementing NPI, both in the scope of prevention and cure, are due to the fact that there are many diseases for which we still do not have a cure, such as Alzheimer's dementia, multiple sclerosis or fibromyalgia. By selecting those NPI that have more scientific evidence and applied by health or non-health personnel, it is intended to improve quality of life, slow down deterioration, relieve pain or restore health at a lower economic and environmental cost whilst complying with the Hippocratic maxim "first, do no harm". There are many NPI currently managed, which are used in most known conditions, to support specific treatment or as a single therapy. Further studies on NPI to improve their safety and efficacy are advisable.

**Keywords:** iatrogenesis, integrative medicine, non-pharmacological interventions, non-pharmacological treatments

## **1. Introduction**

Non-pharmacological interventions (NPI) are part of the chapter on therapeutics in the health sciences. Together with pharmacotherapy, ionising or non-ionising radiation, surgery and rehabilitative medicine they comprise the procedures used to prevent and treat diseases.

Non-pharmacological treatments (NPT) are used for many unconventional treatments in integrative medicine.

The need to use NPI is justified because it is a valid option if indicated as a preventive or curative measure. Side effects of medications are avoided, health costs are brought down and there is no significant environmental impact.

The use of medicines has entailed an important change for humankind. No one doubts the benefits of antimicrobials, vaccines, anti-inflammatories, analgesics, opotherapy and specific medicines for each health problem. Modern surgery has been possible thanks to the development of anaesthetics, anticoagulants and a large

#### *Alternative Medicine - Update*

number of medicines that make it possible for each intervention to be performed. Many material and human resources have been devoted to the study of numerous drugs and a powerful pharmaceutical industry (PI) has developed which occupies the highest echelons in the economy of developed countries.

Although there are many benefits provided by PI and they continue to contribute to the health of humankind, a series of problems that have arisen due to the so-called medicalization of life must be taken into account [1].

Prescribing is far from being totally scientific and suffers from serious shortcomings for various reasons such as commercial interests, deficiencies in clinical trials and regulatory bodies, ethics and environmental problems. Sometimes as many medicines are prescribed as the client has symptoms, whereby it invites a follow-up for possible drug interactions and side effects [2].

Greater prescription of medicines (polypharmacy) is associated with poorer quality of life and higher morbidity. In some developed countries, iatrogenic drugs have displaced accidents as the third or fourth leading cause of death after cardiovascular disease and cancer [3].

The criteria of the prescribing physician, whether primary or specialised care, is important to avoid interactions, overdose, duplicates and other problems that may contribute to the onset of side effects. In addition, the criteria must avoid pressures from the PI and act with a cost criterion; effectiveness, safety and environmental


#### **Table 1.**

*Irregular pharmaceutical industry practices (taken from Goldacre and completed by A. Ursa).*

#### *Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*

sustainability. Due to this latter aspect, NPI should be taken into account since, in principle, they are more environmentally sustainable than medicines.

Evidence-based medicine (EBM) is the current benchmark when it comes to performing a healthcare intervention. Its influence also extends to the design of clinical trials and their reporting.

Since the onset of the 21st century, independent scientists from multinational pharmaceutical companies have denounced the inappropriate practices of the PI. **Table 1** shows some of the irregular practices carried out by the PI for financial purposes, their consequences and solutions according to Ben Goldacre [4].

During the medical procedure, all health professionals when prescribing within the scope of their competence, must choose the best therapeutic option for their client, always bearing in mind the NPI. The reality, however, is different because the future doctor is educated in the prescription of drugs. Because the current medical paradigm requires rapid, accurate and symptomatic actions. However, the side effects of the medicines also need to be tackled. Because of this, a powerful PI has been developed with major economic interests, the medicine has been overvalued and research, development and innovation (RDI) are targeted at these interests and not at NPI [5].

The PI generally spends more on marketing and marketing of medicines than on research [6].

Although it is true that the whole process that entails the launch of a new medicine on the market is lengthy and expensive, the PI often opts for a false innovation. That is how "me too" drugs arrive on the market [7], molecules similar to others in use, enantiomers, racemic mixtures, etc. The PI brings out "me too" drugs when the end of their drug patents approaches. These novelties that are not such, are usually expensive, not superior to the old drugs and are a source of major revenues for the PI [8].

**Table 2** shows some methods used by researchers to obtain favourable results in clinical trials according to Sackett, Oxman, Smith, Peiró and Peralta [9].


#### **Table 2.**

*Methods used to obtain favourable results in clinical trials [9].*

The PI only finances research projects most likely to yield positive results. This breaches the uncertainty principle that establishes that the patient should be included in a CT only if there is substantial uncertainty about which treatment will benefit them the most [9].

The publishers that own the medical journals where the CT are published depend on the PI, since drug advertising, special issues, reprints, etc. are a source of revenue [10]. If an author publishes an unfavourable criticism against a drug or PI, he runs the risk of not receiving income for the above concepts [9].

The fact that certain medicines are included in a clinical practice guide (CPG) is of major interest to the PI, since these guidelines are drawn up by experts for their use [11]. A study published in JAMA in 2002 found a high number of financial relationships between CPG experts and PI. Serious omissions were found in the declarations of conflicts of interest [9].

Conflicts of interest and potential biases in the publication of scientific-medical research have cast doubt on the credibility of the PI [9].

According to Peter Gotzsche, from the University of Gopenhage and director of the Nordic Cochrane Centre, the PI "does not work to improve health, but to obtain the maximum benefits" and to do this "extorts, commits fraud, breaches legislation and lies" [3].

## **2. Non-pharmacological interventions in the health sciences**

#### **2.1 Concept and generalities**

Non-pharmacological interventions (NPI) or non-pharmacological therapies (NPT) are defined as any non-chemical intervention, which is theoretically supported, targeted and replicable, performed on a patient or caregiver and potentially capable of obtaining a relevant benefit [12].

The adoption of a healthy lifestyle is perhaps the best NPI as it will contribute to better health, more life enjoyment and reduce, except for contingencies, health costs. Thus, the ideal place to recommend NPI, as a preventive and/or curative measure is Primary Health Care, in line with the Declaration of Alma Ata of 1978 [13] and ratified 40 years later in Astaná in 2018 [14].

A large number of the techniques used in physiotherapy such as massage, kinesitherapy, etc., manual techniques (joint manipulations, chiropractic, etc.), various techniques used in psychotherapy, yoga, meditation, and others framed under the term non- conventional medical therapies (NCMT) such as acupuncture, moxibustion, homoeopathy, etc., belong to the NPT chapter. Many act by stimulating the body's healing power, sometimes because they stimulate the production of biogenic amines, neuropeptides, stimulate natural defences, produce neuroprotection, etc., which contributes to homeostasis [15].

Although herbal medicine or treatment with medicinal plants forms part of the treatments used in NCMT, it is not included in this section since it deals with chemical substances. This does not mean that they should not be used but rather that it would be desirable to supplement NPT with medicinal plants of proven efficacy and safety. Homoeopathic preparations, however, do fall under the NPT heading, since after several dilutions the original substance is not observed.

NPT seek to relieve symptoms and improve quality of life, which is why they are widely used in the management of dementias, especially Alzheimer's dementia, both in institutions and at home. Applied exclusively or in combination with drugs, they aim to slow down the course of the disease [16].

*Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*

NPT should meet safety and efficacy standards [17] and for this, studies and meta-analyses have had to be performed for scientific validation, as required by evidence-based medicine according to Sackett et al. [18].

Unfortunately, there is not always a company or entity that finances many of these studies. Therefore, there are fewer studies published than those offered by the PI.

Although NPT are used above all in the field of Gerontology, in many other disciplines they also have both preventive and curative applications, either alone or in combination with other therapies.

#### **2.2 NPT in the field of social and healthcare assistance**

NPT began to be applied systematically for dementia, both in institutionalised patients (nursing homes, day care centres) and in their homes. The aim was to, alleviate these processes, since there is no curative treatment [19]. NPT in the field of social and health care are called psychosocial interventions (PSI).

In the 1980s, support programmes for caregivers of dementia patients, whether they were family members or individuals, needed to be performed. In recent years there has been a need to extend these programmes to professional caregivers [19].

Since the last century there have been several attempts to classify PSI. With regard to validating PSI in Alzheimer's dementia, experts recommend basing their actions on systematic reviews and meta-analyses.

Alzheimer's relatives' patient associations consider the areas of intervention in terms of cognitive, functional, emotional and comprehensive aspects.

Some intervention programmes (IP) used in the field of Alzheimer's disease are listed in **Table 3** according to Gárate Olazábal [20].


These interventions can be performed either individually or in groups. Those carried out individually are more effective.

#### **Table 3.**

*Intervention programmes focused on Alzheimer's disease (taken from Gárate Olazábal and completed by A. Ursa).*

The Montessori-Based Dementia Programming (MBDP) method enables adults with dementia to be given tasks initially designed solely for children. Dr. Cameron Camp and the Myers Research Institute are pioneers in the MBDP system, which began to be used in the late 1990s. It is applied at advanced stages and consists of performing scheduled activities based on activities of daily life (ADL). To achieve this, he uses cognitive rehabilitation techniques such as task division, guided repetition, progression from simple to complex, and progression from concrete to abstract. When applied properly, it improves motor skills and basic functional abilities within a reasonable period of time (included in the Barthel index) [21].

Many other NPI can be performed in the social health field and as a first choice, for common pathologies such as insomnia [22], anxiety and stress [23], etc.

Support groups, education techniques and cognitive-behavioural training, counselling and case management, and prevention of physical and/or chemical restraints have been devised among other interventions to reduce the morbidity associated with caring for these patients [24]. This is for the caregiver, whether family or non-family, due to the major burden that falls upon them.

#### **2.3 NPT in the cardiovascular system**

Cardiovascular diseases (CVD) are the most common cause of mortality in Western countries and involve high health costs. Arteriosclerosis develops insidiously over many years and its clinical manifestations appear when the disease is advanced. The CVD burden has grown in recent decades, in parallel to an increased prevalence of risk factors such as obesity, smoking, type 2 diabetes mellitus and high blood pressure [25]. Prevention of CVD involves adopting a healthy lifestyle and intervening on biochemical modifiable factors, etc., by means of pharmacological and/or non-pharmacological treatments.

In recent years, a preventive strategy has been developed in clinical practice based on what is known as cardiovascular rehabilitation (CVR), which is defined according to the World Health Organisation as "the set of activities necessary to ensure people with cardiovascular diseases, an optimal physical, mental and social condition that allows them to occupy by their own means as normal a place as possible in society" [26]. A team of professionals is required to perform CVR, it has relatively little implementation and according to cost-effectiveness studies it is favourable [27].

The prevention of such common pathologies as arterial hypertension is based on dietary advice, practice of physical exercise appropriate to each situation [28], stress control, emotional management and avoiding both legal and illegal drugs.

Many other cardiovascular diseases can be treated as first intention with NPT or as an accompaniment to pharmacological treatment. **Table 4** shows some of these pathologies, NPT and the healthcare professional who applies this.

It would be desirable to implement cardiovascular pathology NPI in health systems to reduce the side effects of medication, polypharmacy, improve quality of life and reduce health costs.

#### **2.4 NPT in the respiratory system**

Chronic obstructive pulmonary disease (COPD) and asthma are common respiratory diseases and in many cases, they go undiagnosed, reduce quality of life and represent a high health cost.

NPT is essential in COPD patients. However, this treatment is sometimes not given adequate importance. Patients diagnosed with COPD should benefit from

*Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*


**Table 4.**

*Some CVD and their non-pharmacological approach.*

comprehensive care services (CCS), which are an articulated set of standardised actions aimed at meeting the COPD patient's health needs, considering the environment and particular circumstances. Pulmonary rehabilitation (PR) is one of the essential components of non-pharmacological treatment in COPD. NPT is used as an adjunct to drug therapy [31] and has been shown to improve functionality [32].

**Table 5** shows the pulmonary rehabilitation plan according to the National Heart, Lung, and Blood Institute (INCPS) [33].

Many other actions have been published for asthma (therapeutic education, massage, music therapy, etc.). However, results are not conclusive.

#### **2.5 NPT in the digestive system**

Gastrointestinal tract diseases are numerous, due to different causes and many are related to an inappropriate lifestyle. In addition to the pharmacological and/or surgical, dietary and psychological treatment from which a benefit can be derived, some are susceptible to improvement with physical treatments such as different applications of hydrotherapy (washes, damp cloths plus drug substance, jets, etc.), physical exercise, relaxation techniques, etc., within the context of personalised medicine.

**Table 6** shows some NPT applied in the most common digestive tract disorders (taken from Schneider and Pizzorno et al. [34, 35]).

In the section on hepatobiliary diseases, there are many accompanying measures to pharmacological, hygienic and dietary treatments that can be performed. Given the characteristics of the book, it is not possible to elaborate in this context.

#### **2.6 NPT in endocrine-metabolic disorders**

Obesity and diabetes mellitus are among the most common of the many endocrinemetabolic disorders in Western countries. Both constitute a public health problem since they cause major morbidity and mortality, which increases the country's health expenditure. The first measure in tackling obesity consists of adopting a healthy lifestyle that enables maintaining an optimal weight. Diet, physical exercise and medical advice should not be lacking when the body mass index is higher than 30. Individualised treatment should take precedence over guidelines or protocols. In the case of type 2 diabetes mellitus, the most common, hygienic-dietary advice needs to be strengthened as an aid to pharmacological treatment if needed [36].

For dyslipidaemia, good results have been achieved with the application of cardio-healthy diets, especially for secondary dyslipidaemia [37].


#### **Table 5.**

*Pulmonary rehabilitation plan according to the INCPS.*


#### **Table 6.**

*NPT in some of the most common digestive tract diseases (taken from the book health by nature and natural medicine manual).*

Physical exercise is the first indication in metabolic syndrome with the aim of reducing abdominal fat deposition and adverse cardiovascular effects. The remaining associated conditions are managed with medical advice, drug therapy, and a correct diet [38].

*Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*

Bone mineral density (BMD) gradually decreases with age and is more evident in women when menopause begins. Physical exercise in conjunction with dietary and hygiene advice has been shown to improve BMD in postmenopausal women [39].

#### **2.7 NPT in musculoskeletal disorders**

Rehabilitation medicine and physiotherapy as members of the health sciences are the paradigm of NPT, since a large part of their actions are based on physical procedures.

Some symptoms and signs that accompany many osteoarticular, neurological, psychiatric and other diseases are the usually associated inflammation and pain. **Table 7** includes some procedures used in rehabilitation medicine and physiotherapy taken from Miranda Mayordomo [40].

The choice between heat and cold treatment is governed by principles and is sometimes applied empirically.

Heat provides transient relief in subacute and chronic inflammatory and traumatic disorders, such as sprains, muscle strains, fibrositis, tenosynovitis, muscle spasms, myositis, lower back pain, neck injuries, various forms of arthritis, arthralgia, neuralgia, etc. Heat increases blood flow, and helps relieve inflammation, oedema and exudates from connective tissue injuries. Heat can be applied either superficially (infrared, hot compresses, paraffin bath, hydrotherapy) or deep (ultrasound). The intensity and duration of physiological effects depend primarily on the temperature of the tissue, the rate of temperature rise, and the area treated [40].

Cold can help relieve muscle spasms, myofascial or traumatic pain and acute inflammation (sprain, low back pain, etc). As of a certain temperature, cold induces


#### **Table 7.**

*Some physical therapies used in rehabilitation/physiotherapy (taken from Miranda Mayordomo's book, Medical Rehabilitation and completed by A. Ursa).*

a certain local anaesthesia (cryotherapy). Cold is usually used for a few hours after a muscle or tendon injury, up until evaluation [40].

Hydrotherapy in rehabilitative medicine is used in many conditions. Stirred hot water stimulates blood flow and debrides burns and wounds. This treatment is performed in a Hubbar tank with water between 35.5°C and 37.7°C. Full immersion in water heated to between 37.7°C and 40°C can also help relax muscles and relieve pain. Hydrotherapy is particularly useful for range-of-motion exercises [41, 42].

Electrotherapy in rehabilitative medicine plays an important role in many locomotor system disorders, either exclusively or as a complement to other techniques [43].

The various areas of physiotherapy, such as paediatric, respiratory, pelvic floor, neurological or sports - with their preventive, curative and rehabilitative approach – tackle numerous conditions that I do not address given the characteristics of this chapter.

#### **2.8 NPT in neuropsychiatry**

Although pharmacological therapy has played an important role in psychiatric conditions since its introduction, sometimes it is difficult to comply with the therapy due to the disease itself, due to side effects or due to access to medication, either during hospitalisation or domiciliary care. Because of this, a series of nonpharmacological techniques and procedures to treat the most common neuropsychiatric pathologies have been developed. NPT in psychiatry should generally be used before drug treatment. However, the reality is usually different. **Table 8** reports some of the most frequent techniques and procedures used in the most common neuropsychiatric conditions, taken from various authors.

There are NPT for neurological conditions such as migraine, multiple sclerosis, Parkinson's disease, etc., which have been implemented in recent years. These require further studies for their validation**.**

#### **2.9 NPT in sense organ conditions**

Among the eyeball conditions, the Bates method for improvement of vision without glasses is notable. This work was published for the first time in 1919 in the USA [53].

After several years of observation, Dr. William H. Bates (1860–1931), an American ophthalmologist, devised some exercises to restore normal vision in some eye problems and dispense with using glasses. He started from the hypothesis that


#### **Table 8.**

*Most common neuropsychiatric pathologies and non-pharmacological approach (compiled by A. Ursa).*

*Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*


#### **Table 9.**

*Some Bates method exercises (taken from Roselló's book see well without glasses).*

the tension caused by certain visual habits were the main cause of poor eye vision. This method helps patients become aware of use of their visual organ by means of a series of eye and non-eye exercises. **Table 9** shows some of these exercises according to Roselló [54].

The Bates method is indicated for all vision refractive problems such as myopia, astigmatism, hyperopia and presbyopia. It is contraindicated in the event of macular degeneration, eye infection or eyeball tumour [53].

In the last few years, the Bates method has been taught on postgraduate courses at some European universities and recommended by some ophthalmologists. However, there are detractors of the method [55].

#### **3. Summary and conclusions**

Although we cannot dispense with medicines, medical protocols and guidelines must be urgently reviewed. This is because most are based on medicines as a first line treatment option.

Bioethics committees in clinical trials should be comprised of independent staff. Conflicts of interest in scientific publications should be more closely monitored.

The acquisition of a healthy lifestyle must be promoted through Primary Healthcare, as part of a primary prevention programme.

Non-pharmacological treatments (NPT) are especially indicated for chronic diseases. However, many acute conditions can also benefit.

Numerous conditions of most bodily systems can be treated with NPT. Implementing this modality would contribute to reducing the adverse effects of medicines, bring healthcare expenditure down and lead to environmental sustainability.

*Alternative Medicine - Update*

## **Author details**

Andrés J. Ursa Herguedas1,2,3

1 Institute of Integrative Medicine, Valladolid, Spain

2 Staff Lecturer (Healthcare Area) of the Spanish Regional Government of Castilla y León, Spain

3 Member of the Dr. Ramón y Cajal Illustrious Academy of Health Sciences, Madrid, Spain

\*Address all correspondence to: ajursa@educa.jcyl.es

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*

## **References**

[1] Illich I. Medical nemesis. The expropriation of health. Random House USA Inc. 1988. ISBN: 978-0394712451

[2] Mendoza Patiño, N.; de León Rodríguez, J.A.; Figueroa Hernández, J.L. Pharmacological Iatrogenesis. Journal of the Faculty of Medicine UNAM, 2004; 47(1)

[3] Gotzsche, PC. (2014). Medicines that kill and organized crime. Los Libros del Lince. Barcelona (Spain). ISBN: 978-8415070450

[4] Goldacre, B. (2013). Bad Pharma. Ed. Paidos Ibérica. Barcelona (Spain). ISBN: 978-8449328435

[5] Cobos LP & Sánchez RP. Nonpharmacological therapies in Primary Care. Notebooks of the Antonio Esteve Foundation n° 3. Spanish Network of Primary Care, 2004. Barcelona. ISBN: 8493339067

[6] Viña-Pérez G, & Debesa-García F. The pharmaceutical industry and the promotion of medicines. A reflection required. Gaceta Médica Espirituana, 2017; 19 (2) ISSN: 1608-8921

[7] Angell, M. The truth about the drug companies. How they deceive us and what to do about it. Random House Trade Paperbacks. 2005. ISBN: 978-0375760945

[8] Lexchin J. & Cosgrove LA. Can you rely on the drugs that your doctor prescribes? The Conversation, 13 June 2018. Available in: https:// theconversation.com/can-you-rely-onthe-drugs-that-your-doctor-prescribes-98128?utm\_source=twitter&utm\_ medium=twitterbutton

[9] Cañás M. Evidence-based medicine, conflicts of interest, and clinical trials. In: Drugs today: old and new challenges. Edition 1st. Chapter 6. Publisher.

UNESCO: 145-200. 2009 ISBN: 978-8588233317

[10] Mintzberg H. Patent nonsense: evidence tells of an industry out social control. Canadian Medical Association Journal. 2006; 175 (4) DOI: 10.1503/ cmaj.050575

[11] Alonso P. & Bonfill X. Clinical practice guidelines: search and critical assessment. Radiology, 2007; 49 (1) DOI: 10.1016/S0033-8338 (07) 73712-8

[12] Olazarán J, Clare L et al. Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy. Alzheimer Dem 2006; 2 [Suppl 1]: S28. DOI: 10.1159/000316119

[13] World Health Organization. International Conference on Primary Health Care. Series "Health for all" n° 1. Geneva, Switzerland, 1978 ISBN: 92 4 354135 8

[14] World Health Organization. Global Conference on Primary Health Care. Astana, Kazakhstan, October 2018. https://www.who.int/primary-health/ conference-phc

[15] Martínez-Sánchez LM et al. Use of alternatives therapies, current challenge in the management of pain. Journal of the Spanish Society of Pain, 2014; 21 (6) DOI: 10.4321/ S1134-80462014000600007

[16] Muñiz R., & Olazarán J. Map of non-pharmacological therapies for Alzheimer's dementias. Technical initiation guide for Professionals. Document prepared for the State Reference Center (CRE) for Attention to People with Alzheimer's Disease and other Dementias of Salamanca by the Maria Wolff Foundation and the International Non Pharmacological Therapies Project. Salamanca, Spain, 2009.

[17] Olazarán-Rodríguez J. et al. Efficacy of non-pharmacological therapies in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 2010; 30: 161-178 DOI: 10.1159/00316119

[18] Rodríguez Germán M & Sánchez Mejía A. Evidence Based Medicine: a guide to make right and democratic decisions. Rev Med Hered, 2009; 20 (2) ISSN: 1018-130X

[19] Olazarán-Rodríguez J. et al. Psychological and behavioral symptoms of dementia: prevention, diagnosis and treatment. Rev Neurol 2012; 55 (10): 598-608. PMID: 23143961

[20] Gárate Olazábal M. Therapeutic interventions based on daily life and user preferences. Matia Gerontological Institute Foundation. Basque government. Spain

[21] Camp CJ. Origins of Montessori programming for dementia. Nonpharmacol Ther Dement. 2010; 1 (2): 163-174. PMID: 23515663; PMCID: PMC3600589.

[22] Baidos Noriega R et al. Nursing and non-pharmacological treatment for the management of insomnia. Quarterly Electronic Journal of Nursing, 2019; 54 ISSN: 1695-6141

[23] Crespo Nalgo MD. Nursing intervention in relaxation techniques is effective in treating anxiety. Rev Presencia, 2016.; 102: 6-12. Available in: http://www.index.f.com/p2o/n23/ p10922.php (consulted on 18.9.2020)

[24] Tips for Family Caregivers of People with Alzheimer's. Pascual Maragall Foundation and Barcelona Beta Brain Research Center. Barcelona, Spain

[25] Cortés-Bergoderi M. et al. Availability and characteristics of cardiovascular rehabilitation programs in South America. J. Cardio-Pulm. Rehabil. Prev., 2013; 33: 33-34. DOI: 10.1097/HCR.0b013e318272153e.

[26] Brown RA. Rehabilitation of patients with cardiovascular diseases. Report of a WHO expert committee. World Health Organ Tech Rep Ser., 1964; 270: 3-46 ISBN: 924120270X

[27] López-Jiménez et al. Consensus on cardiovascular rehabilitation. Uruguayan Journal of Cardiology, 2013; 28 (2). Online versión ISSN 1688-0420

[28] Briones Arteaga EM. Physical exercises in the prevention of arterial hypertension. Medisan, 2016; 20 (1): 35-41 Online version ISSN 1029-3019.

[29] Placido R & Mebazaa. Nonpharmacological treatment of acute heart failure. Spanish Journal of Cardiology, 2015; 68 (9): 794-802. DOI: 10.1016/j.rec.2015.05.006

[30] Schneider E. (2003). Health by nature. Vol. 1. Ed. Safeliz. Madrid (Spain), 2003. ISBN: 84-7208-116-8

[31] Pleguezuelos E. et al. Recommendations on nonpharmacological therapies in chronic obstructive pulmonary disease of the Spanish COPD Guide. Archives of bronchopneumology, 2018; 54 (11): 568-575 DOI: 10.11016/j. arbres.2018.06.001

[32] Kuzmar I. et al. Effects of pulmonary rehabilitation in patients with COPD/asthma: a systematic review. Venezuelan Archives of Pharmacology and Therapeutics., 2017; 36 (6): 179-185. ISSN: 0798-0264

[33] National Heart, Lung, and Blood Institute. Bethesta (EEUU). Available in: http://www.nhlbi.nih.gov/health/ health-topics/topics/copd/

[34] Schneider E. Health by nature. Tomo 2. Ed Safeliz. Madrid. Spain, 2003 ISBN: 84-7208-117-6

[35] Pizzorno, JE.; Murray, MT.; Joiner-Bey, H. Natural Medicine Manual. 2nd *Non-Pharmacological Interventions in Preventive, Rehabilitative and Restorative Medicine DOI: http://dx.doi.org/10.5772/intechopen.94187*

edition. Elsevier España. Barcelona. Spain. 2009 ISBN: 978-8480064664

[36] Reyes Sanamé FA et al. Type 2 diabetes mellitus current treatment. Scientific Medical Mail, 2016; 20 (1) online version ISSN: 1560-4381

[37] Ballesteros-Álvaro AM. et al. Non-pharmacological interventions in dyslipidemia. Available in: https://www.saludcastillayleon. es/investigacion/es/bancoevidencias-cuidados/ano-2012. ficheros/1204811-Intervenciones%20

[38] Aguirre-Urdaneta, MA et al. Physical activity and metabolic syndrome: Citius-Altius-Fortius. Advances in diabetes, 2012; 28 (6): 123- 130. DOI: 10.1016/j.avdiab.2012.10.002

[39] Molina E et al. Variation of bone mineral density induced by exercise in postmenopausal women. International Scientific Medical Journal of Physical Activity and Sport, 2015; 15 (59): 527- 541. ISSN: 1577.0354

[40] Miranda Mayordomo J.L. Medical Rehabilitation. Ed. Medical Classroom Toledo (Spain), 2004 ISBN: 978-84788853762

[41] Saz Peiró P. & Ortiz M. Hydrotherapy. Professional pharmacy, 2005; 19 (4): 84-89

[42] Armijo Valenzuela M. & San Martín Baicacoa J. Curas Balnearias y climáticas. Talasoterapia y Helioterapia. Ed Complutense University. Madrid, Spain, 2009 ISBN: 8474914833

[43] Rodríguez Martín JM. (2009). Electrotherapy in physiotherapy. Panamerican Medical Ed. 2009 ISBN: 978-8479035631

[44] Galve JJ. Naturopathic clinical guide to anxiety and panic attacks. Medicina Naturista, 2008; 2 (3): 57-64. ISSN. 1576-3080

[45] Ursa Herguedas AJ. Meditation as a preventive and curative practice in the national health system. Medicina Naturista, 2018: 12 (1): 47-53. ISSN. 1576-3080

[46] Ursa Herguedas AJ y Ursa Bartolomé MI. Contact with nature as a preventive measure for diseases and a therapeutic resource. Medicina Naturista, 2019; 13 (1): 28-33. ISSN: 1576-3080

[47] Díez González et al. Giving priority to nom-pharmacological treatment in insomnia. Community nursing SEAPA, 2016; 4 (2): 30-43

[48] Baides Noriega R. et al. Nursing and non-pharmacological treatment for the management of insomnia. Global Nursing, 2019; 54 DOI:10.6018/ eglobal.18.2.322311

[49] Alonso López RN et al. Physical exercise as a non-pharmacological treatment measure for depression. In: Quality of life, caregivers and intervention for the improvement of health, 2017. ISBN: 978-84 697 3989 8

[50] Tuunainen A et al. Light therapy for non-seasonal depression. Cochrane Database of Systematic Reviews, 2004, Issue 2. DOI: 10.1002/14651858. CD004050.pub2

[51] Jiménez de la Fuente A., Effects of equestrian therapies in people with cerebral palsy. Spanish Journal of Disability, 2017; 2 DOI: 10.5569/2340-5104.05.02.09

[52] Acebes de Pablo A & Giraldez-Hayes A. The role of music therapy in the treatment of attention deficit hyperactivity disorder: an exploratory study. Medicina Naturista, 2019; 13 (1): 15-20 ISSN: 1576-3080

[53] Bates WH. The Bates method to improve vision without glasses. Ed.

Paidos. Barcelona. Spain, 2006. ISBN: 978-84-493-1924-2

[54] Roselló, R. See well without glasses. Ed. Oceano Ambar. Barcelona, Spain, 2007 ISBN: 978-8475565095

[55] Elliot BD. The Bates method, elixirs, potions and other cures for myopia: how do they work? Ophtalmic Physiol Optics., 2014; 33: 75-77. DOI: 10.111/ opo.12034

Section 7 Diabetes

## **Chapter 11**

## Antidiabetic Activities of *Terminalia* Species in Nigeria

*Franklyn Nonso Iheagwam, Omoremime Elizabeth Dania, Happiness Chijioke Michael-Onuoha, Olubanke Olujoke Ogunlana and Shalom Nwodo Chinedu*

## **Abstract**

*Terminalia* species are well recognised in traditional medicine. They are known for producing fruits and nuts which are edible and possess pharmacotherapeutic properties. They also have ornamental purposes in urban areas where they are found. These species are used by traditional healers in the treatment and management of diabetes mellitus, its complications and other related ailments that are involved in the pathophysiological process of this disease. Research has been extensively done to validate these antidiabetic claims scientifically as well as understand the mechanism and mode of antidiabetic action. This chapter proposes to highlight the antidiabetic activities of *Terminalia* species found in Nigeria.

**Keywords:** *Terminalia* species, antidiabetic, Nigeria, diabetes mellitus, mode of action, mechanism, traditional medicine

## **1. Introduction**

Diabetes mellitus (DM) is a chronic metabolic disorder that is not only affecting various populations worldwide but also poised on affecting the developing nations of the world much more than developed countries [1, 2]. The International Diabetes Foundation (IDF) reported a diagnosis of over 400 million people living with diabetes and postulated an estimated increase to over 600 million people by the year 2040 in a worldwide survey [3, 4]. The report also shows that diabetes accounts for a death every 6 seconds [3]. In a recent study, it was observed that the total reported cases of people affected by DM had increased by 10 million in the subsequent survey carried out by IDF over the next year [5].

DM is a heterogeneous metabolic disorder and is difficult to classify. However, DM has been categorised into three major types based on the pathologic process. Type 1 diabetes mellitus (T1DM), also known as childhood/early-onset diabetes or insulin-dependent DM, is characterised by insulin deficiency as a result of β-cell dysfunction, degeneration and degradation by the immune system [6]. Type 2 diabetes mellitus (T2DM), also known as adult/late-onset diabetes or non-insulin-dependent DM has insulin secretion and insulin resistance (IR) as its major characteristics [7]. Gestational diabetes mellitus (GDM) has glucose intolerance in pregnant women as its major characteristic. It is as a result of the β-cells inability to meet up with the insulin demand in pregnant women without a previous diagnosis of diabetes [8].

Diabetologists have a few other categories, such as tropical DM and Type 3 diabetes mellitus (T3DM). The former is thought to have a relationship with malnutrition [8], while the latter is a suggested mechanistic link to Alzheimer's disease via inflammatory response and other mechanisms resulting in the pathophysiologic changes relating diabetes to dementia [3]. However, there is little information on the rarer forms of diabetes, such as secondary diabetes, mitochondrial diabetes, maturity-onset diabetes of the young, and latent autoimmune diabetes of adults [9].

## **1.1 Risk factors**

Physical inactivity or sedentary lifestyle, excessive alcohol, overweight, obesity and unhealthy diet intake are modifiable DM risk factors [10]. Family history, hypertension, history of previously impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), advancing age, history of GDM, ethnicity and genetic makeup are some unmodifiable risk factors. However, various researchers have reported that novel risk factors such as short sleep duration [11], noise pollution [12] and environmental toxins [13] contribute to the causal pathways which lead to diabetes. Trade and agricultural production policies are thought to contribute to both individual and societal level risk factors [14].

## **2. Diabetes mellitus in Nigeria**

## **2.1 Epidemiology**

The transition from infectious diseases to non-communicable diseases as leading causes of death is fast becoming a growing epidemiological trend and public health dichotomy in Sub-Saharan African countries [15]. In Africa, there is a 1% estimated prevalence of diabetes in rural areas while in urban areas, the range is from 5–7% [16]. Nigeria accounts for about one-sixth of Africa's population [1]. The national prevalence of diabetes, which was less than 1% between 1960 and 1990, has risen from 2.2% in 1997 to 5% in 2013 [17]. However, the current prevalence may currently be as high as between 8 and 10% [9], with 4.83% recorded for patients aged 20 and above, accounting for over 3 million people currently living with this condition [18]. This observation makes her the country with the highest number of people living with diabetes and IFG in Africa [19]. Epidemiological statistics show that Nigeria is responsible for one in every five reported sub-Saharan case of diabetes, with a steep increase in the prevalence of this disease from the rural areas to members of the high socio-economic population [9]. Continuous urbanisation, the increasing population and poor economy, will further drive the incidence and burden of diabetes upwards in Nigeria [1, 2, 20]. T2DM appears to be the majority of the DM burden in Nigeria with T1DM accounting for less than 10% of DM cases [21], while tropical DM makes up less than 1% [8]. Lifestyle factors such as sedentary lifestyle, cigarette smoking and generous consumption of alcohol are known risk factors linked to the development of T2DM. Obesity has been reported to be a major contributor to approximately 55% of diagnosed cases of T2DM, with a prevalence of 3.3 to 18% [2]. It has also been associated with several life-threatening diseases such as cardiovascular disease (CVD), several cancer types, as well as reduced quality of life [22, 23]. Diabetes-related morbidity and mortality have been reported to be high in different locations in Nigeria with 105,091 diabetes-related deaths recorded as at 2013 and most patients reported to have been suffering from T2DM [10].

## **2.2 Management**

Given the current DM epidemic and its projected consequences, effective population-based intervention identification has become a priority public health strategy in Sub-Saharan Africa [24]. In Nigeria, insulin, oral glucose-lowering drugs, diet and exercise are used in the management of DM. Complementary and alternative medicine such as concoctions, infusions, tinctures and herbal supplement is also used [1]. Inability to use insulin syringe, the high cost of therapy, few options in the Nigerian market and poor policies on DM management are a few challenges affecting insulin treatment [25]. The medications used in the management of diabetes become less effective over time as most patients do not achieve normal glycaemic control with their use [26], and thus have resulted to possible second-line medications to achieve the normal glycaemic target [27]. Despite the high cost of medication as well as the inability to maintain normal glycaemic control for an extended period, the use of polytherapy to achieve sufficient glucose control is a common feature in Nigeria [28]. Challenges such as needle phobia, hypoglycaemia, drug-associated side effect and cost of medication have made over 46% of diabetic patients opt for complementary and alternative medicine, with *Vernonia amygdalina* which is also known as "bitter leaf" being most utilised [29]. The school of thought that diabetics should abstain from carbohydrate rich meals has led to the intake of monotonous food like unripe plantain, beans and wheat rich diet [1, 30]. This challenge occurs due to the absence of a taste-appealing standardised diet for diabetics as well as their dietary requirements influenced by economic status, religious and cultural beliefs [1].

## **3.** *Terminalia* **species as medicinal plants**

Medicinal plants (MPs) are a rich source of natural products with potential medical interest. There is an increased interest in the use of medicinal plants and their products as a result of their reported wide range application. Asides their application, they are the richest bioresource of modern medicines, nutraceuticals, food supplements, chemical entities for synthetic drugs, pharmaceutical intermediates, folk medicines and drugs of traditional systems of medicine [31]. These plants are also known to contain different plant secondary metabolites such as tannins, flavonoids, saponins alkaloids, terpenoids and phenols, which are responsible for numerous characteristics such as colour, flavour, smell and texture in various parts of these plants. These plant metabolites are also known for their pharmacological mechanism of actions in the treatment, management and prevention of diseases [32].

*Terminalia* genus has about 250 flowering tree species which belong to the Combretaceae family. They are found in the tropics of Australia, Asia, Africa and South America. The bark of many *Terminalia* species appear to be cracked from the stem, the branches are arranged in a stepwise manner with the leaves appearing large and leathery on the tips of shoots. The appearance of the leaves is responsible for the genus nomenclature *Terminalia* which is a derivative of the Latin word Terminus. The fruits of most *Terminalia* species are edible with deep red, yellow or black pulp colouration and hard nuts [33]. Extensive research has shown that *Terminalia* species are a rich source of phytocompounds ranging from flavonoids (gallic acid, ellagic acid, quercetin, hesperetin), steroids (β-sitosterol, terminic acid), tannins (punicallin, terchebulin, castalagin), vitamins (α-tocopherol), carotenoids (lutein) and others [33–35]. The various reported pharmacological activities such as antimalarial, antioxidant, antibacterial, antifungal, cardiovascular effects, antidiarrhoeal, analgesic, anti-inflammatory, hypolipidaemic, hypoglycaemic, antiprotozoal, antiviral, wound healing, antimutagenic and anticancer properties have been attributed to these compounds [33].

## **3.1** *Terminalia* **species in Nigeria**

There are about ten species of *Terminalia* found in Nigeria, namely; *Terminalia altissima* (Synonym: *superba*)*, Terminalia avicennioides, Terminalia brownii, Terminalia catappa, Terminalia glaucescens, Terminalia ivorensis, Terminalia laxiflora, Terminalia macroptera, Terminalia mollis and Terminalia schimperiana* [33, 36, 37]*.* These species have been reported to be pharmacologically active with antimicrobial, antimycobacterial, wound healing, gastroprotective, antimalarial, antioxidant, antifungal, anthelmintic, antibacterial, antifungal, antiviral, analgesic, radical scavenging, hepatoprotective, anticancer, antimutagenic, antiaging, aldose inhibitory, antiplasmodial, cytotoxic, antipsychotic, sedative, analgesic, anti-inflammatory, trypanocidal, hypolipidaemic, antioxidant, antimycoplasmal and androgenic, properties as shown in **Table 1** [34, 35, 38–42].

*Terminalia* species in Nigeria, have numerous application in the treatment and management of ailments among the various traditional medicine systems of different ethnic groups. Different parts are utilised by traditional healers to treat cholera, malaria, typhoid, hepatitis, stomach ache, tuberculosis, leprosy, diarrhoea, skin diseases, gastritis, hyperglycaemia, diabetes, gonorrhoea, wounds, epilepsy and catarrh [56–58]. They are also used as tonic, laxative and chewing sticks [26, 59, 60].

Several reports have highlighted some pharmacological properties of *Terminalia* species in Nigeria, such as its antimicrobial properties, antibacterial property, antiinflammatory action, anti-HIV, hypoglycaemic, modulatory properties, analgesic, wound healing, antioxidant and radical scavenging activity, hepatoprotective, anticancer, anti-trypanocidal, antimutagenic and antiaging properties.

Nigeria's vegetation is made up of forests, savannahs and montane land. All others but the latter are further divided into three parts which have ensured the wide distribution of these species across the country. This variation in the country's vegetation has not only made these *Terminalia* species specific to Nigeria and West Africa, but accounts for the difference in their evolutionary relationship, development and pharmacologic activity. Upon assessment of the phylogenetic relationship on www.phylogeny.fr [61], using the available nucleic acid sequence of the *Terminalia* species that were deposited in National Center for Biotechnology Information (NCBI) GenBank, it was observed that species that were closely related such as *T. catappa* and *T. glaucescens* as well as *T. superba* and *T. avicennioides* were located in the same vegetative region of the country (**Figure 1**). Irrespective of their evolutionary differences, it was observed that there were conserved regions that were similar in the deposited genetic sequence of the *Terminalia* species in Nigeria showing over 94% sequence similarity (**Figure 2**).

#### **3.2 Pharmacologic antidiabetic activities of Nigerian** *Terminalia* **species**

The pharmacologic antidiabetic activity of *Terminalia* species have been reported in different climes using various *in vitro, in vivo* and *in silico* techniques in mice, rat, rabbit and humans to elucidate them. Nonetheless, in Nigeria, there is a paucity of data on the antidiabetic mode of action and mechanisms of *Terminalia* spp. despite its abundance. However, there are antidiabetic reports of these species from neighbouring countries with similar vegetation.


#### *Antidiabetic Activities of* Terminalia *Species in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.94474*

**Table 1.**

*List of* Terminalia *species found in Nigeria and their reported ethnopharmacological activity.*

### *3.2.1 In vitro assessments*

The crude aqueous and hydroethanolic leaf extracts of *T. catappa* from Nigeria have been reported to inhibit both α-glucosidase and α-amylase effectively. Mixed and non-competitive mode of inhibition were the mechanisms of action elucidated for the extracts [35]. This finding was further corroborated by *in silico* studies, in which the identified bioactives showed preferential binding to the active site than the allosteric site of α-glucosidase and α-amylase [35]. The α-amylase inhibitory property of crude methanol extract and solvent fractions of *T. brownii* stem bark was lower than that of acarbose as reported in [62]. When compared with some

#### **Figure 1.**

*Phylogenetic tree of some selected* Terminalia *species in Nigeria.*

other medicinal plants, crude ethanol, aqueous and hydroethanolic extracts of *T. superba* root exhibited better inhibitory action on α-amylase activity than their respective counterparts [63]. For α-glucosidase and lipoxygenase inhibitory activity, the potency of dichloromethane, methanol and solvent fractions of *T. macroptera* leaves have been established to be more potent than acarbose and quercetin respectively [40].

High-throughput techniques were used to identify isolated bioactive compounds (gallic acid and methyl gallate) from *T. superba* stem bark dichloromethane extract, which exhibited very high inhibitory property on α-glucosidase activity [64]. Other isolates such as arjunic acid and glaucinoic acid from *T. glaucescens* stem barks and chebulagic acid, corilagin and narcissin from *T. macroptera* leaves are reported to exhibit significant β-glucuronidase, α-glucosidase and 15-lipoxygenase inhibitory activity respectively [40, 65].

## *3.2.2 In vivo assessments*

The pre-administration of methanol-methylene chloride extract of *T. glaucescens* leaves have been reported to confer protective properties in mice against streptozotocin-induced diabetes effects [66]. *T. schimperiana* root bark extracts have been reported to be effective in reducing blood glucose and excess body lipids in alloxaninduced diabetic rats [67, 68]. The hypoglycaemic activity of *T. catappa* leaves has also been recorded [69]. The leaves have also been associated with a significant decrease of C-reactive protein, interleukin-6, fibrinogen and inflammatory markers associated with diabetes in rats when compared with other non-steroidal anti-inflammatory drugs [70]. In male rats fed with *T. catappa* drupe and seeds supplemented-diets for fourteen days, they were found to have exhibited enhanced sexual behaviour and biomarkers relevant to erectile dysfunction that were initially suppressed by streptozotocin-induced diabetic state [71]. Most research on the antidiabetic assessment of *Terminalia* species in Nigeria have reported the beneficial effect in rats and mice. Interestingly, in Ref. [72], *T. catappa* intake was found to illicit negative herb-drug effect by increasing the activity of transaminases concomitantly enhancing the adverse hepatic effects of antidiabetic drugs such as pioglitazone and atorvastatin.

#### *Antidiabetic Activities of* Terminalia *Species in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.94474*


**Figure 2.**

*Multiple sequence alignment of some selected* Terminalia *species in Nigeria.*

## **4. Conclusion**

The Nigerian *Terminalia* genus is made up of species that possess antidiabetic principles. This activity has been related to the presence and synergistic action of phytochemicals such as tannins, phenolics, terpenoids, flavonoids and other active bioconstituents. The species of this genus in Nigeria can provide great medicinal value to the country and its populace. However, most of the antidiabetic pharmacological assessment has been done only on *Terminalia catappa, Terminalia glaucescens* and *Terminalia schimperiana.* Moreso, high throughput analytical techniques and equipment can be utilised to identify and isolate novel phytocompounds that may be of therapeutic value in the management and treatment of diabetes. It is also imperative to identify the sequence of all Nigerian *Terminalia* species to understand better the genetic relationship, genetic variability, intraspecific variability and traits heritability in vegetative and floral characters of these species.

It was also observed that the majority of antidiabetic assessments of these *Terminalia* species were done *in vitro*, in rats and mice. Nonetheless, more *in vivo* studies should be carried out to identify the molecular mechanisms involved in its antidiabetic activity. Nigeria is the most challenged sub-Saharan nation with diabetes, a public health issue that needs to be tackled urgently. Hence, there is a need to increase translational research and explore the antidiabetic assessment of these *Terminalia* species directly on patients to extrapolate results that will be beneficial to the Nigerian public health system.

## **Acknowledgements**

The authors acknowledge Olawumi Toyin Iheagwam for proofreading the manuscript.

## **Conflict of interest**

The authors declare no conflict of interest.

## **Author details**

Franklyn Nonso Iheagwam1 \*, Omoremime Elizabeth Dania1 , Happiness Chijioke Michael-Onuoha<sup>2</sup> , Olubanke Olujoke Ogunlana1 and Shalom Nwodo Chinedu1

1 Department of Biochemistry and Covenant University Public Health and Wellness Research Cluster (CUPHWERC), Covenant University, Ota, Nigeria

2 Centre for Learning Resources, Covenant University, Ota, Nigeria

\*Address all correspondence to: franklyn.iheagwam@covenantuniversity.edu.ng

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Antidiabetic Activities of* Terminalia *Species in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.94474*

## **References**

[1] Ogbera AO, Ekpebegh C. Diabetes mellitus in Nigeria: The past, present and future. World Journal of Diabetes. 2014;**5**(6):905-911

[2] Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: A review of current trends. Oman Medical Journal. 2012;**27**(4):269-273

[3] Boles A, Kandimalla R, Reddy PH. Dynamics of diabetes and obesity: Epidemiological perspective. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2017;1863(5):1026-36.

[4] Pesta DH, Goncalves RLS, Madiraju AK, Strasser B, Sparks LM. Resistance training to improve type 2 diabetes: Working toward a prescription for the future. Nutrition and Metabolism. 2017;**14**:24

[5] Uloko AE, Musa BM, Ramalan MA, Gezawa ID, Puepet FH, Uloko AT, et al. Prevalence and risk factors for diabetes mellitus in Nigeria: A systematic review and meta-analysis. Diabetes Therapy. 2018;**9**(3):1307-1316

[6] Enk J, Mandelboim O. The role of natural cytotoxicity receptors in various pathologies: Emphasis on type I diabetes. Frontiers in Immunology. 2014;**5**:4

[7] Li W, Yuan G, Pan Y, Wang C, Chen H. Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: A review. Frontiers in Pharmacology. 2017;**8**:74

[8] Azevedo M, Alla S. Diabetes in SubSaharan Africa : Kenya, Mali, Mozambique, Nigeria, South Africa and Zambia. International Journal of Diabetes in Developing Countries. 2016;**28**(4):101-108

[9] Fasanmade OA, Dagogo-Jack S. Diabetes care in Nigeria. Annals of Global Health. 2015;**81**(6):821-829

[10] Oputa R, Chinenye S. Diabetes in Nigeria – A translational medicine approach. African Journal of Diabetes Medicine. 2015;**23**(1):7-10

[11] Heianza Y, Kato K, Fujihara K, Tanaka S, Kodama S, Hanyu O, et al. Role of sleep duration as a risk factor for type 2 diabetes among adults of different ages in Japan: The Niigata wellness study. Diabetic Medicine. 2014;**31**(11):1363-1367

[12] Dzhambov AM. Long-term noise exposure and the risk for type 2 diabetes: A meta-analysis. Noise & Health. 2015;**17**:23-33

[13] Taylor KW, Novak RF, Anderson HA, Birnbaum LS, Blystone C, DeVito M, et al. Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: A national toxicology program workshop review. Environmental Health Perspective. 2013;**121**(7):774-783

[14] Jaacks LM, Siegel KR, Gujral UP, Narayan KMV. Type 2 diabetes: A 21st century epidemic. Best Practice and Research Clinical Endocrinology and Metabolism. 2016;**30**(3):331-343

[15] Hult M, Tornhammar P, Ueda P, Chima C, Bonamy AE, Ozumba B, et al. Hypertension, diabetes and overweight: Looming legacies of the Biafran famine. PLoS One. 2010;**5**(10):1-8

[16] Kengne AP, Amoah AGB, Mbanya J. Cardiovascular complications of diabetes mellitus in sub-Saharan Africa. Circulation. 2005;**112**:3592-3601

[17] International Diabetes Federation. IDF diabetes atlas 2017 [Available from: http://www.diabetesatlas.org/ component/attachments/?task=downlo ad&id=116

[18] Jackson IL, Adibe MO, Okonta MJ, Ukwe CV. Knowledge of self-care among type 2 diabetes patients in two states of Nigeria. Pharmacy Practice. 2014;**12**(3):1-10

[19] Isara AR, Okundia PO. The burden of hypertension and diabetes mellitus in rural communities in southern Nigeria. Pan African Medical Journal. 2015;**20**:103-109

[20] Ekwunife OI, Ezenduka CC, Uzoma BE. Evaluating the sensitivity of EQ-5D in a sample of patients with type 2 diabetes mellitus in two tertiary health care facilities in Nigeria. BMC Research Notes. 2016;**9**:24-28

[21] Muhammad F. Diabetes: A silent killer in Nigeria. Jundishapur Journal of Chronic Disease Care. 2020;**9**(4):e105702

[22] Akarolo-Anthony SN, Willett WC, Spiegelman D, Adebamowo CA. Obesity epidemic has emerged among Nigerians. BMC Public Health. 2014;**14**:455-463

[23] Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990 – 2010: A systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2224-60.

[24] Oyeyemi AL, Adegoke BO, Oyeyemi AY, Deforche B, De Bourdeaudhuij I, Sallis JF. Environmental factors associated with overweight among adults in Nigeria. International Journal of Behavioral Nutrition and Physical Activity. 2012;**9**:32

[25] Ogbera AO, Kuku SF. Insulin use, prescription patterns, regimens and costs - a narrative from a developing country. Diabetology and Metabolic Syndrome. 2012;**4**:50

[26] Kadiri M, Ojewumi A, Agboola D, Adekunle M. Ethnobotanical survey of plants used in the management of diabetes mellitus in Abeokuta, Nigeria. Journal of Drug Delivery and Therapeutics. 2015;**5**(3):13-23

[27] Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017;**6736**(17):1-13

[28] Yusuff KB, Obe O, Joseph BY. Adherence to anti-diabetic drug therapy and self management practices among type-2 diabetics in Nigeria. Pharmacy World and Science. 2008;**30**(6):876-883

[29] Ogbera AO, Dada O, Adeyeye F, Jewo PI. Complementary and alternative medicine use in diabetes mellitus. West African Journal of Medicine. 2010;**29**:158-162

[30] Udogadi NS, Onyenibe NS, Abdullahi MK. Dietary management of diabetes mellitus with focus on Nigeria. International Journal of Diabetes Research. 2019;**2**(1):26-32

[31] Ncube NS, Afolayan AJ, Okoh AI. Assessment techniques of antimicrobial properties of natural compounds of plant origin: Current methods and future trends. African Journal of Biotechnology. 2008;**7**(12):1797-1806

[32] Sarin R. Useful metabolites from plant tissue cultures. Biotechnology. 2005;**4**(2):79-93

[33] Cock IE. The medicinal properties and phytochemistry of plants of the genus Terminalia (Combretaceae). Inflammopharmacology. 2015;**23**:203-229

[34] Iheagwam FN, Okeke CO, DeCampos OC, Okere DU, Ogunlana OO, Chinedu SN. Safety evaluation of Terminalia catappa Linn (Combretaceae) aqueous leaf extract: Sub-acute cardio-toxicopathological studies in albino Wistar rats. Journal

*Antidiabetic Activities of* Terminalia *Species in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.94474*

of Physics: Conference Series. 2019;**1299**(1):012109

[35] Iheagwam FN, Israel EN, Kayode KO, De Campos OC, Ogunlana OO, Chinedu SN. GC-MS analysis and inhibitory evaluation of Terminalia catappa leaf extracts on major enzymes linked to diabetes. Evidence-based Complementary and Alternative Medicine. 2019;**2019**:6316231

[36] Idemudia OG. Terpenoids of Nigerian Terminalia species. Phytochemistry. 1970;**9**(11):2401-2402

[37] Zhang XR, Kaunda JS, Zhu HT, Wang D, Yang CR, Zhang YJ. The genus Terminalia (Combretaceae): An ethnopharmacological, phytochemical and pharmacological review. Natural Products and Bioprospecting. 2019;**9**(6):357-392

[38] Dwevedi A, Dwivedi R, Sharma YK. Exploration of phytochemicals found in Terminalia sp. and their antiretroviral activities. Pharmacognosy Reviews. 2016;**10**(20):73-83

[39] Okey E, Madueke A, Ossai E, Anosike A, Ezeanyika L. Antidiarrhoeal properties of the ethanol extract of Terminalia glaucescens roots on castor oil-induced diarrhoea in wistar rats. Tropical Journal of Natural Products Research. 2020;**4**(8):446-450

[40] Pham AT, Malterud KE, Paulsen BS, Diallo D, Wangensteen H. α-Glucosidase inhibition, 15-lipoxygenase inhibition, and brine shrimp toxicity of extracts and isolated compounds from Terminalia macroptera leaves. Pharmaceutical Biology. 2014;**52**(9):1166-1169

[41] Anand AV, Divya N, Kotti PP. An updated review of Terminalia catappa. Phamacognosy Review. 2015;**9**(18):93-98

[42] Agbedahunsi J, Anao I, Adewunmi C, Croft S. Trypanosidal properties of Terminalia ivorensis a. Chev (Combretaceae). African Journal of Traditional, Complementary and Alternative Medicines. 2006;**3**(2):51-56

[43] Onyekwelu JC, Stimm B. Terminalia superba. In: Stimm B, Roloff A, Lang UM, Weisgerber H, editors. Enzyklopädie der Holzgewächse: Handbuch und Atlas der Dendrologie: Wiley; 2004. p. 1-12.

[44] Adeyemi FO, Jimoh AA, Wilson UN. A review of mechanical strength properties of some selected timbers in Nigeria. The International Journal of Science and Technoledge. 2016;**4**(2):9-15

[45] Adewuyi AM, Akangbe YT, Animasaun DA, Durodola FA, Bello OB. Terminalia avicennioides as a potential candidate for pharmaceutical industry: A review. Research Journal of Pharmaceutical Biological and Chemical Sciences. 2015;**6**(2):748-754

[46] Aliyu H, Suleiman M, Ahmed A, Chiezey N, Ahmed A. Terminalia avicennioides Guill & Perr (Combretaceae): Pharmacology and phytochemistry of an alternative traditional medicine in Nigeria: Mini review. Journal of Pharmacognosy and Natural Products. 2018;**4**(2):1000152

[47] Salih EY, Julkunen-Tiitto R, Lampi AM, Kanninen M, Luukkanen O, Sipi M, et al. Terminalia laxiflora and Terminalia brownii contain a broad spectrum of antimycobacterial compounds including ellagitannins, ellagic acid derivatives, triterpenes, fatty acids and fatty alcohols. 227, 82-96. Journal of Ethnopharmacology. 2018;**227**:82-96

[48] Berinyuy BE, Abdullahi M, Kabiru AY, Ogbadoyi EO. Comparative anti-malarial and toxicological properties of the stem bark extracts

of Nauclea latifolia and Terminalia glaucescens against plasmodium berghei-infected mice. Iranian Journal of Toxicology. 2020;**14**(1):9-18

[49] Fahmy NM, Al-Sayed E, Singab AN. Genus Terminalia: A phytochemical and biological review. Medicinal and Aromatic Plants. 2015;**4**(5):1-22

[50] Chika PJ, Sakpere AM, Akinropo MS. Effect of pretreatments on germination of seeds of the timber plant, Terminalia ivorensis and Mansonnia altissima (a. Chev.). Notulae Scientia Biologicae. 2020;**12**(2):334-340

[51] Ogunwande IA, Ascrizzi R, Flamini G. Essential oil composition of Terminalia ivorensis a. Chev. Flowers from northern Nigeria. Trends in Phytochemical Research. 2019;**3**(1):77-82

[52] Haidara M, Haddad M, Denou A, Marti G, Bourgeade-Delmas S, Sanogo R, et al. In vivo validation of anti-malarial activity of crude extracts of Terminalia macroptera, a Malian medicinal plant. Malaria Journal. 2018;**17**(1):1-10

[53] Usman S, Agunu A, Atunwa S, Hassan S, Sowemimo A, Salawu K. Phytochemical and anti-inflammatory studies of ethanol extract of Terminalia macroptera Guill. & Perr. (Combretaceae) stem bark in rats and mice. Nigerian Journal of Pharmaceutical Research. 2017;**13**(2):147-156

[54] Muraina IA, Adaudi AO, Mamman M, Kazeem HM, Picard J, McGaw LJ, et al. Antimycoplasmal activity of some plant species from northern Nigeria compared to the currently used therapeutic agent. Pharmaceutical Biology. 2010;**48**(10):1103-1107

[55] Awotunde OS, Adewoye SO, Dhanabal PS, Hawumba J. Subacute toxicity study of aqueous root extract of Terminalia schimperiana in male Wistar rats. Toxicology Reports. 2019;**6**:825-832

[56] Khan ME, Bala LM, Maliki M. Phytochemical analyses of Terminalia schimperiana (Combretaceae) root bark extract to isolate stigmasterol. Advanced Journal of Chemistry-Section A (Theoretical, Engineering and Applied Chemistry). 2019;2(4):327-34.

[57] Pham AT, Malterud KE, Paulsen BS, Diallo D, Wangensteen H. DPPH radical scavenging and xanthine oxidase inhibitory activity of Terminalia macroptera leaves. Natural Product Communications. 2011;6(8):1934578X1100600819.

[58] Akinyemi KA. Antibacterial screening of five Nigerian medicinal plants against S. typhi and S. paratyphi. Journal of the Nigerian Infection Control Association. 2000;**3**(1):30-33

[59] Ezuruike UF, Prieto JM. The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations. Journal of Ethnopharmacology. 2014;**155**(2):857-924

[60] Ogundiya MO, Kolapo AL, Okunade MB, Adejumobi JA. Assessment of phytochemical composition and antimicrobial activity of Terminalia glaucescens against some oral pathogens. Electronic Journal of Environmental, Agricultural and Food Chemistry. 2009;**8**(7):466-471

[61] Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, et al. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Research. 2008;36(W465-W469).

[62] Alema NM, Periasamy G, Sibhat GG, Tekulu GH, Hiben MG. Antidiabetic activity of extracts of Terminalia brownii Fresen. Stem bark in mice. Journal of Experimental Pharmacology. 2020;**12**:61-71

*Antidiabetic Activities of* Terminalia *Species in Nigeria DOI: http://dx.doi.org/10.5772/intechopen.94474*

[63] Momo CEN, Ngwa AF, Dongmo GIF, Oben JE. Antioxidant properties and α-amylase inhibition of Terminalia superba, Albizia sp., Cola nitida, Cola odorata and Harungana madagascarensis used in the management of diabetes in Cameroon. Journal of Health Science. 2009;**55**(5):732-738

[64] Wansi JD, Lallemand MC, Chiozem DD, Toze FAA, Mbaze LMA, Naharkhan S, et al. α-Glucosidase inhibitory constituents from stem bark of Terminalia superba (Combretaceae). Phytochemistry. 2007;**68**(15):2096-2100

[65] Rahman AU, Zareen S, Choudhary MI, Akhtar MN, Ngounou FN. Some chemical constituents of Terminalia glaucescens and their enzymes inhibition activity. Zeitschrift für Naturforschung B. 2005;**60**(3):347-350

[66] Njomen GB, Kamgang R, Soua PR, Oyono JL, Njikam N. Protective effect of methanol-methylene chloride extract of Terminalia glaucescens leaves on streptozotocin-induced diabetes in mice. Tropical Journal of Pharmaceutical Research. 2009;**8**(1):19-26

[67] Khan M, Bala L, Igoli J. Isolation of caccigenin and investigation of anti-diabetic properties of tropical almond (Terminalia schimperiana) root bark extracts on albino rats. Journal of Chemical Society of Nigeria. 2019;44(3).

[68] Ojewumi A, Kadiri M. Phytochemical screening and antidiabetic properties of Terminalia schimperiana leaves on rats. International Journal of Green and Herbal Chemistry. 2014;**3**(4):1679-1689

[69] Koffi NG, Yvetten FN, Noel ZG. Effect of aqueous extract of Terminalia catappa leaves on the glycaemia of rabbits. Journal of Applied Pharmaceutical Science. 2011;**1**(8):59-64 [70] Ben EE, Asuquo AE, Owu DU. Comparative effect of aspirin, meloxicam and Terminalia catappa leaf extract on serum levels of some inflammatory markers in alloxan induced diabetic rats. Asian Journal of Research in Biochemistry. 2019;**4**(1):1-10

[71] Adebayo AA, Oboh G, Ademosun AO. Almond-supplemented diet improves sexual functions beyond Phosphodiesterase-5 inhibition in diabetic male rats. Heliyon. 2019;**5**(12):e03035

[72] Ezuruike U, Prieto JM. Assessment of potential herb-drug interactions among Nigerian adults with type-2 diabetes. Frontiers in Pharmacology. 2016;**7**:248

## **Chapter 12**

## Some Folk Antidiabetic Medicinal Herb of Himachal Pradesh

*Monika Rana and Meenakshi Rana*

## **Abstract**

The Prevalence of Diabetes Mellitus (DM) is increasing day by day at an alarming worldwide. As per the statics of International Diabetic Federation, currently worldwide approximately 463 million adults (20–79 years) affected with diabetes that is expected to increase rise to 700 million by 2045. Diabetes and its complications imposes an economic loss to people with diabetes and their families, and to health systems and national economy. Diabetes is a complex disease which link with multiple of factors. Present reviewdocument the information of traditional used Antidiabetic plants by the inhabitants of Nadaun, District Hamirpur, Himachal Pradesh, India. During the survey 31 Medicinal Plants have been documented on the basis of information collected from the respondents of the study area.

**Keywords:** diabetes, ayurveda, Himachal Pradesh, traditional medicines

## **1. Introduction**

Diabetes mellitus (DM) is a serious lifelong disease characterized by elevation of blood glucose level in the body resulting from the defects in insulin secretion and insulin resistance [1, 2]. The global diabetes prevalence for all age-groups was estimated to be 9.3% in 2019 rising to 10.2% in 2030. The prevalence is lower in rural than the urban areas [3]. The total number of people with diabetes is estimated to rise from 171 million in 2000 to 366 million in 2030. Among DM, about 90 percent of population affected with Type 2 DM [4]. In addition to hyperglycemia, diabetes also associated with various vascular complications, which are the major causes of morbidity and death in diabetic Patients [5].

In Ayurveda Diabetes Mellitus (DM) is referred to as Madhumeha (means sweet urine disease). Madhumeha consists of two words-'madhu and meha' where 'madhu' denotes sweetness and 'meha' stands for urination. In Ayurveda, plants are known to be excellent source of drugs. Plant based drugs have been in use against various diseases since time immemorial. There is large number of drugs of herbal origin mentioned in Ayurveda texts, which were advised for treatment of Madhumeha [6]. Even today a huge number of population in the world used the medicinal plants for the treatment of Diabetes Mellitus [7]. As the incident and severity of Diabetes is increasing worldwide, it imposes an huge economic loss to people with diabetes and their families, and to health systems and national economy [8]. The importance of traditional plant medicines from the last decade goes on increasing with both medical and economic implications [9]. On the other hand the chemically synthetic hypoglycaemic agents used for the treatment of diabetes are not only expensive but also cause various complications and side effects to the health [10].

## **2. Materials and methods**

Nadaun is a small town in Hamirpur district, located in central Himachal Pradesh, India, right near Beas River. The Townis situated between 76°18′ –76°49′ East longitude and 31°52′30″ North Latitudes. The track is hilly covered by Shivalik range and the elevation varies from 450 to 11,000 meters. As per the census of India 2011, it has a population of 4430. The Climate is characterized by an intensely hot summer, a pleasant cold season. The summer season from March to about middle of June is followed by the south-west monsoon season from mid-June to the end of September. October and first half of November constitute the post-monsoon period. The cold season is from mid-November to February. The minimum and maximum day time temperature varies between 20° and 42°. People in this region can easily understand Hindi and can communicated in that language.

In order to documentation of the record frequent field surveys were conducted many time (**Figure 1**). A questionnaire contains the details of the plants, parts used, medicinal uses and mode of preparation of remedies is structured and informal talks were employed to gain the information about the use of plants as Antidiabetic. Any statistical survey is not used in the given study.

**Figure 1.** *Field survey.*

## **3. Result and discussion**

Ethnobotany may be defined as the scientific study of the dynamic relationship between various plant and people. The present study highlighted the traditional herbal medicine used for the treatment of diabetes in the particular selected study area. During the survey, around 50 people mostly old aged person selected randomly for the study. Information of plants along with their common name, useful part, time of availability, mode of preparation and consuming is documented (**Table 1**). All the plants are photographed as a record (**Figure 2**). Most of the recorded plants are available from the wild growth, and some are cultivated by the local villagers. Mostly plants materials are preserved in dry powder form as these are available only in a particular season. Various methods of preparation of these herbal remedies were recorded during the study. The preparation were also consumed by the people in the form of juice, churna, chutney and chapattis. In the present study we found that people have a close relationship with the nature for their health care. As the importance of ethnobotanical studies goes on increase day


#### *Some Folk Antidiabetic Medicinal Herb of Himachal Pradesh DOI: http://dx.doi.org/10.5772/intechopen.94188*

#### *Alternative Medicine - Update*


#### **Table 1.**

*Antidiabetic plants recorded from Nadaun, Hamirpur District.*

*Some Folk Antidiabetic Medicinal Herb of Himachal Pradesh DOI: http://dx.doi.org/10.5772/intechopen.94188*

#### **Figure 2.**

*Plants used traditionally for the treatment of diabetes.*

by day, it is mandatory preserve the information's about the knowledge of folklore medicinal plants which is use by local communities before it is permanently disappear.

*Alternative Medicine - Update*

## **Author details**

Monika Rana1 \* and Meenakshi Rana<sup>2</sup>

1 School of Pharmacy, Maharaja Agrasen University, Baddi, Himachal Pradesh, India

2 GSS Sachdeva, Kharar, SAS Nagar, Punjab, India

\*Address all correspondence to: sairana.rana43@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Some Folk Antidiabetic Medicinal Herb of Himachal Pradesh DOI: http://dx.doi.org/10.5772/intechopen.94188*

## **References**

[1] Classification of diabetes mellitus, World Health Organization , Geneva, 2019.

[2] Tan SY, Sim YJ, Wong SS, *etal*. Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. 2019; 13(1):364-372.

[3] Saeedi P,Petersohn I *etal*. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice. 2019; 157: 107843.

[4] Wild S, Sicree R *etal*. Global Prevalence of Diabetes. Diabetic Care. 2004; 27:1047-1053.

[5] Surya S, Salam AD, Tomy DV *etal*. Diabetes mellitus and medicinal plants-a review. Asian Pacific Journal of Tropical Disease. 2014; 4(5):337-347.

[6] Jaiswal KM, Shah C. A Review Of Diabetes Mellitus And Herbs In Ayurveda. Imperial Journal of Interdisciplinary Research. 2016; 2(3): 514-520.

[7] E Martins. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety.2014;4:177.

[8] Seuring T, Archangelidi O, Suhrcke M. The Economic Costs of Type 2 Diabetes: A Global Systematic Review. 2015;33(8):811-831.

[9] Rang HP, Dale MM. The Endocrine System Pharmacology. 2nd ed. Harlow, UK: Longman; 1991: 504-8

[10] Mahady GB. Global harmonization of herbal health claims. Journal of Nutrition. 2001;131:1120S-3S

## **Chapter 13**
