**3. Arthritis drug design**

There are globally 1.3 billion cases of musculoskeletal disorders and over 121,000 deaths from such disorders, as well as nearly 139 million disability-adjusted life years, or the number of years lost due to ill-health, disability or early death [43]. Globally, the proportion cases in are led by the low back pain (37%); followed by "other"

**249**

**Table 7.**

*Polyphenols, Spices and Vegetarian Diet for Immunity and Anti-Inflammatory Drug Design*

(21%); osteoarthritis (19%); neck pain (18.4%); gout (2.6%); and rheumatoid arthritis (1.3%). These proportions changed little from 1990. Surgery and the NSAID- Non steroidal anti-inflammatory drugs- are costly and cause adverse effects such as gastric and cardiovascular issues. The herbal medicines are perhaps effective and in growing demand and even exported much, as dietary supplements that are common globally and many having positive outcomes at least in the short term [44, 45]. But herbs they use are and are often adulterated such as Shalaki (Indian Frankincense/Olibanum, *Boswellia serrata*) or Guggulu (Indian Myrrh, *Commiphora wightii,* [46]. Hence, sustainable ingredients from farm are needed such as Drumstick (*Moringa olifera* tree leaves), rich in calcium and highly exported [47]. Glusosamine, a popular health supplement in arthritis is a sea shell product [48]. So it needs a vegetarian option due to the growing trend of veganism globally. Spices can address this as they contain the bio- actives to relive Arthritic pain and inflammation- Vitamin A, C & K, polypohenols, Omega 3 fatty acids, and minerals Calcium, Magnesium, Iron and Zinc [29]. Even in India, about 40% the elderly may be Arthritis affected, it is said in the study by All Indian Institute of Medical Science in metros such as Delhi AIMS [49]. Bioactive ingredient levels are low in the general market samples of spices such as Black pepper (Piperine- 2-4%), Coriander (Quercetin- 0.12%), Turmeric (Curcumin- 2-3%), as the critical agri-inputs to increase the polyphenol content e.g. Potassium for Curcumin by 50% in Turmeric [50, 51]. Higher Potassium inputs also enhances oil content in Coriander [52], for instance. So improving agro-tech-

We demonstrate here the comparative advantage of spices over the standards drug for the treatment of arthritis, to illustrate the alternative approach to drug discovery. Hence, we performed docking study at Rasa Life. Co., (www.rasalsi.com) Pune during 2020 on the key bioactive compounds important spices w.r.t. COX2 (cyclooxygenase) active site (PDB ID 5IKR obtained from PDBsum). **Table 7** shows that the 4 spice ingredients have closeby values and high theraupetic potential are

> **Site & activity (interactions)- (PDB id 5f19)**

Pepper Piperine (53) SER530 & ARG 120 (2) −9.99 Good activity, high

TRP 387 & ASN 382 (2) ALA199, TRP 387 and ASN 382, TRP387, TYR385(A)

(1)

SER530 & MET522 (2)

TYR385- Good activity (1)

385(Chain A)

Fenugreek Diosgenin (20) HIS214 (outside site) −6.80 outside, not feasible

**Binding energy (kcal/mol)** **Remarks**

probability

probability

high probability

probability

−9.94 Stable, high

−8.66 -"-

−7.34 -"-

−6.33 Stable, high

−7.51 Stable, good activity,

*DOI: http://dx.doi.org/10.5772/intechopen.97661*

nology can enhance the bioactive potential of the spices.

**Spice Ingredient** 

Coriander Apigenin (20)

High potential

Less scope

**(conformation)**

Quercetin

Turmeric Curcumin (35) TYR 385- good activity

Ginger 8-shogaol (40) Amino acid residues-

Clove Eugenol SER 530 & TYR

10- Gingerol (40)

*Docking study results of Spices active ingredients in COX-2.*

#### *Polyphenols, Spices and Vegetarian Diet for Immunity and Anti-Inflammatory Drug Design DOI: http://dx.doi.org/10.5772/intechopen.97661*

(21%); osteoarthritis (19%); neck pain (18.4%); gout (2.6%); and rheumatoid arthritis (1.3%). These proportions changed little from 1990. Surgery and the NSAID- Non steroidal anti-inflammatory drugs- are costly and cause adverse effects such as gastric and cardiovascular issues. The herbal medicines are perhaps effective and in growing demand and even exported much, as dietary supplements that are common globally and many having positive outcomes at least in the short term [44, 45]. But herbs they use are and are often adulterated such as Shalaki (Indian Frankincense/Olibanum, *Boswellia serrata*) or Guggulu (Indian Myrrh, *Commiphora wightii,* [46]. Hence, sustainable ingredients from farm are needed such as Drumstick (*Moringa olifera* tree leaves), rich in calcium and highly exported [47]. Glusosamine, a popular health supplement in arthritis is a sea shell product [48]. So it needs a vegetarian option due to the growing trend of veganism globally. Spices can address this as they contain the bio- actives to relive Arthritic pain and inflammation- Vitamin A, C & K, polypohenols, Omega 3 fatty acids, and minerals Calcium, Magnesium, Iron and Zinc [29].

Even in India, about 40% the elderly may be Arthritis affected, it is said in the study by All Indian Institute of Medical Science in metros such as Delhi AIMS [49].

Bioactive ingredient levels are low in the general market samples of spices such as Black pepper (Piperine- 2-4%), Coriander (Quercetin- 0.12%), Turmeric (Curcumin- 2-3%), as the critical agri-inputs to increase the polyphenol content e.g. Potassium for Curcumin by 50% in Turmeric [50, 51]. Higher Potassium inputs also enhances oil content in Coriander [52], for instance. So improving agro-technology can enhance the bioactive potential of the spices.

We demonstrate here the comparative advantage of spices over the standards drug for the treatment of arthritis, to illustrate the alternative approach to drug discovery. Hence, we performed docking study at Rasa Life. Co., (www.rasalsi.com) Pune during 2020 on the key bioactive compounds important spices w.r.t. COX2 (cyclooxygenase) active site (PDB ID 5IKR obtained from PDBsum). **Table 7** shows that the 4 spice ingredients have closeby values and high theraupetic potential are


#### **Table 7.**

*Docking study results of Spices active ingredients in COX-2.*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

Reasons for the Increased Use of CAM and Dietary Supplements are

b.increased contact with other cultures that traditionally use CAM.

c.Renewing d interest in formerly countercultural ideologies, such as

d.the perception that CAM is easier to understand, safer, and less expensive than

f. a growing recognition that many factors contribute to health and well-being.

Nevertheless, spices and herbs have great potential in future as depicted below

There are globally 1.3 billion cases of musculoskeletal disorders and over 121,000 deaths from such disorders, as well as nearly 139 million disability-adjusted life years, or the number of years lost due to ill-health, disability or early death [43]. Globally, the proportion cases in are led by the low back pain (37%); followed by "other"

with in the example of an anti-inflammatory drug design excercise.

With the growing use of the herbal medicines, safety concern is emerging due to the issues such as adulteration, quality and adverse reaction [41]. Hence, World Health Organization (WHO), devised a Traditional Medicine New Strategy (2006–2013) with 3 key health priorities [42], as most countries have traditional/

a.the increased availability of information on the Internet

e.distrust of and frustration with the health care system.

4.Arthritis- 3.5%,

5.Anxiety- 2.8%,

6.Cholesterol- 2.1%,

10.Insomnia- 1.4%.

environmentalism.

conventional medications.

herbal medicine policy to mainstream it

b.non-communicable diseases and

c.universal health coverage.

**3. Arthritis drug design**

a.mental health,

7.Head or chest cold- 2%,

8.Other musculoskeletal- 1.8%,

9.Severe headache or migraine- 1.6%,

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viz. Piperine (Black Pepper, −9.99 Kcal/ mol) 'Apigenin' (Coriander, −9.63) and 'Curcumin' (Turmeric, −8.66 with the stability than methotrexate (−8.6), the standard NSAID [53]. The values are also higher than the synthetically designed 'best' molecule- i.e. 4-(4-methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d] pyrimidine discovered in the Saudi Arabia [53] or isatin (benzohydrazide) [54]. Ginger (−7.51 kcal/mol- 8-Shagaol), and Diosgenin from Fenugreek had the lower than the threshold values (−6.8) so are not considred here here. Other traditional medicine such as Ayurvedic top used herbs such as Behera (*Terminalia bellerica*) & Herra (*T. chebula*) have also shon high anti-inflammatory potential against COX-2 [55].

The earlier tests of herbal ayurvedic medicines in Arthritis treatment yielded encouraging results in Pune city [56], India, and in USA [57]. So this approach needs further exploration. Quercetin from Coriander & Onion, peppers has higher docking score (−12) than even the active ingredients of the commonest herbal drugs Guggul & Shalaki (<10) [58]. Quercetin is also found to be more effective than even aspirin or celecoxib in the inflammation markers cyclooxygenase (COX) that are vital in cancer biology vide studies in Russia [59] and also in India [60]. Hence, the use of these novel molecules in the arthritis context may be found safe, effective and sustainable.

#### **4. Conclusion**

Immunity decline is a major cause of the pandemics in the last century and thus inflammation control is a major challenge for healthcare system. Spices and herbs, rich in polyphenols can be vital tool in this regards as they have high antioxidant value and reduce the oxidative damage to the body. Much greater share of vegetarian diet and spices, besides less intensity of packed foods, meat, liquor, Tobacco, refined carbs, soft drinks etc. in India may be driving its higher immunity and lower burden of COVID-19. Pharmacokinetic methods such as molecular docking can be used to design drugs for immunity building and inflammation control. This is shown with the example of Arthritis where Black Pepper, Coriander & Turmeric can provide potent drugs vide docking studies with focus on piperin, quercetin/ apigenin & curcumin.
