**Abstract**

Muscular atrophy is one of disease by the loss of skeletal muscle mass. So, by the loss in muscle often causes rapid muscle atrophy and the occurs during injury and illness its causes immobilization in spinal muscle mass. Usually, the impact factor of the nervous system in musculoskeletal is caused by aging, immobility, malnutrition, medication and even the range of injuries disease impact by the nervous system. To meet the needs needed by the loss of skeletal, we need high total antioxidant from herbal medicine as multifunctional potentially prevention of muscular atrophy condition. Antioxidants are agents that can slow down or prevent oxidation process and protect cells system from the damage of cell by the loss skeletal in muscle mass. One of herbal medicine is *Abelmoschus manihot* L. Medik From Palu of central Sulawesi as a possible multifunctional prevention of Muscular Atrophy, where the total antioxidant value is 3,45 mg/mL.

**Keywords:** total antioxidant, herbal medicine, multifunctional prevention, muscular atrophy

#### **1. Introduction**

Muscular atrophy is one of disease by the loss of skeletal in muscle mass. The muscular atrophy recessive autosomal in neuromuscular with characterized of alpha motor neuron in the spinal cord [1]. The neuromuscular disorders are one factor genetic of infant mortality [2]. The spinal muscular atrophy deletion or mutation the Survival motor neuron 1 (SMN 1 gene), reduction of levels functional survival motor neuron 1 (SMN 1 gene) and also resulting selective death of spinal motor neurons system in a pathway, it's depends by the age of onset, symptoms and maximum function achieved [3]. By the age at the onset it causes at birth: Neuromuscular disease, congenital myotonic dystrophy and spinal muscular atrophy, other causes are systematic septicemia-induced disease, lung damage, intracranial pathologies, infection of the central nervous system, disorders of the peripheral nerves, disease of the neuromuscular junction, Prader-Willi syndrome and drug intoxication during pregnancy or delivery system and after 6 months of age were the neuromuscular disease: spinal muscular atrophy types II and III, polyneuropathies, childhood myasthenia gravis, muscular dystrophies and metabolic myopathy and besides that in other causes were congenital heart disease, malnutrition, rickets, metabolic diseases, nephropathies and lung diseases [4, 5]. The clinical prognosis of

spinal muscular atrophy is variable and depends on types of spinal muscular atrophy continuous spectrum with the age of death by infancy to normal life expectancy condition system on cell pathway system [6]. The Muscular atrophy its described with characterized generalized muscle and atrophy in the proximal limb muscle and phenotype by four grades of severity, where the spinal Muscular Atrophy I, spinal Muscular Atrophy II, spinal Muscular Atrophy III and spinal Muscular Atrophy IV, it's all depended by onset and motor spinal function [7, 8]. The muscular atrophy disease by the control mutation in the homozygous of survival motor neuron α (SMN 1) gene. The skeletal of muscular atrophy it's adverse consequences and the mechanism such as wasting or decrease of injury time. Lack of use in the spinal muscular atrophy and event disease category of spinal muscular atrophy. The spinal muscular atrophy it's usually considered by chronic diseases such as poliomyelitis, Diabetes mellitus, cancer, renal failure or pulmonary obstruction [1].

To activation of spinal muscular atrophy, we need the process to activation of the distinct pathway (ATP) in proteolysis pathway. The condition of spinal muscular atrophy it's depends on the level of muscle protein nutrition system. To reduce the fiber muscle we need synthesis protein to innervate proximal hindlimb muscles and medical motor neurons axial muscles [9]. Mitochondrial is important in skeletal muscle to activation of function and subpopulation involved in cellular functions. Mitochondria play in role key on muscle fibers to the regulation of myonuclear apoptosis and serving uptake the calcium [10]. Mitochondria also continuously produce superoxide radicals and dismutated into hydrogen peroxide (H2O2), where H2O2 is a relatively and diffuse freely with cytosol, it's very important as signaling to the molecule on cell, to affecting multiple control of the cell cycle, uptake to cellular stress response, activation energy metabolism and also to the expression of numerous redox-sensitive genes in spinal muscular atrophy disease [9].

#### **2. Prevalence, incidence and carrier frequency of muscular atrophy**

According to the worldwide about a study into the prevalence and incidence of spinal muscular atrophy, where approximately 1–2 per 100.000 people and incidence around 1 in 10.000 live births have been estimated with the spinal muscular atrophy type I accounting for around 60% of all cases and estimation of the incidence of all types of spinal muscular atrophy of around 10 in 100.000 (1 in 10.000) live birth is cited [11]. Every incidence is a factor from a number of new cases of the disease in a particular time period. The evaluation of the incidence of all type SMA combined it's around 8 per 100.000 live births. The incidence of spinal muscular atrophy type I is around 4–6 in 100.000 and for the type II and III it's a high incidence combined 10,6 per 100.000 and for the gender, it's a nearly even split male and female [12]. The indicated difference of spinal muscular atrophy types is the between ethnicities and differences in health system clinically diagnosed. The prevalence in Indonesia of neuromuscular in RSCM hospital from January – December 2017 is 2,6% of all patients who come to the neurology outpatient ward. The five most who have neuromuscular disorders are neuropathy peripheral, Duchenne muscular dystrophy, spinal muscular atrophy, Guillain barre syndrome and chronic inflammatory demyelinating polyneuropathy [13].

#### **3. Genetics of spinal muscular atrophy**

Spinal muscular atrophy is a defect in survival motor neuron 1 (SMN 1) and it's gene localized to 5q11.2-q13.3). SMN gene (SMN 1 and SMN 2) on chromosome

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*Total Antioxidant from Herbal Medicine as a Possible Tool for the Multifunctional Prevention…*

5q13 and the homozygous deletion of the SMN 1 gene result in Spinal muscular atrophy. Besides that, the SMN 2 gene it produces mostly a shortened, unstable the survival motor neuron mRNA and also to alternative splicing, a small amount of full – length on functional SMN mRNA. The SMN 2 gene is a good prognostic of the spinal muscular atrophy in clinical severity. The clinical severity management of spinal muscular atrophy disease is supportive to increase the survival motor neuron expression levels in motor neurons cells system. So, the management of spinal muscular atrophy depends on increase SMN expression levels in motor

The survival motor neuron 1 gene it should be sequenced mutations if both full SMN 1 present of diagnosis on spinal muscular atrophy is highly, but the SMN 1 gene should be sequenced if the striking typical phenotype, where if sequencing indicates and intact SMN 1 gene of phenotype suggestive of spinal muscular atrophy neurogenic. The survival motor neuron 2 gene should be routinely assessed and it's important to factor system influencing the severity of the spinal muscular

Factor oxidative stress of muscle atrophy it's important to maintenance and quality to the rehabilitation of disease. The skeletal of muscle atrophy need continuously produce oxidants like as a reactive oxygen species (ROS) and reactive nitrogen species (RNS) to an imbalance of skeletal muscle mechanism process. The soluble

. Where, it also needs antioxidant species state such as catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) and the last to imbalance denominated of oxidative stress, it's can produce oxidative damage in lipids,

Deoxyribonucleic acid (DNA) and protein to impairing functional protein factor of

2O 2H H O O <sup>2</sup> 22 2 *SOD* <sup>+</sup>

The skeletal of muscle atrophy could inactivity increase of mitochondrial reactive oxygen species (ROS) production on the ways. The mitochondrial could uptake of calcium and increase mitochondrial levels state of fatty acid hydroperoxides and the last depressed protein could transport into the mitochondria system. So, if the

oxidase 2O NADPH 2O NADP H 2 2

Generation of ROS could uptake of oxygen, activation of NADPH oxidase and to

− ++ <sup>+</sup> →+ + (1)

<sup>+</sup> → + (2)

−

, H2O2 and

**4. Molecular oxidative stress factor of muscular atrophy**

atrophy it's produced different oxidative stress state species such as O2

production of the superoxide anion radical, see the reaction:

is converted to H2O2 (Eq. (2) by SOD

mechanism responsible, it's could increase mitochondrial fission [9].

The observation of muscle mass-specific overexpression of Peroxisome proliferator-activated receptor-y-coactivator-1α (PGC-1α) and the master regulator of mitochondria biogenesis could prevent activation of catabolic system and disuse of muscle atrophy system. The Peroxisome proliferator-activated receptory-coactivator-1α (PGC-1α) is mediated pathway and focuses on the role PGC-1α in the skeletal spinal muscular atrophy system by immobilization system. The Peroxisome proliferator-activated receptor-y-coactivator-1α (PGC-1α) is the master transcription stimulates of mitochondrial biogenesis pathway system with up the regulating system of the nuclear respiratory factors (NRF-1,2) and mitochondrial

*DOI: http://dx.doi.org/10.5772/intechopen.94184*

neurons [3].

OH<sup>−</sup>

atrophy phenotype [1].

cellular system [14].

Where O2

−

*Total Antioxidant from Herbal Medicine as a Possible Tool for the Multifunctional Prevention… DOI: http://dx.doi.org/10.5772/intechopen.94184*

5q13 and the homozygous deletion of the SMN 1 gene result in Spinal muscular atrophy. Besides that, the SMN 2 gene it produces mostly a shortened, unstable the survival motor neuron mRNA and also to alternative splicing, a small amount of full – length on functional SMN mRNA. The SMN 2 gene is a good prognostic of the spinal muscular atrophy in clinical severity. The clinical severity management of spinal muscular atrophy disease is supportive to increase the survival motor neuron expression levels in motor neurons cells system. So, the management of spinal muscular atrophy depends on increase SMN expression levels in motor neurons [3].

The survival motor neuron 1 gene it should be sequenced mutations if both full SMN 1 present of diagnosis on spinal muscular atrophy is highly, but the SMN 1 gene should be sequenced if the striking typical phenotype, where if sequencing indicates and intact SMN 1 gene of phenotype suggestive of spinal muscular atrophy neurogenic. The survival motor neuron 2 gene should be routinely assessed and it's important to factor system influencing the severity of the spinal muscular atrophy phenotype [1].

#### **4. Molecular oxidative stress factor of muscular atrophy**

Factor oxidative stress of muscle atrophy it's important to maintenance and quality to the rehabilitation of disease. The skeletal of muscle atrophy need continuously produce oxidants like as a reactive oxygen species (ROS) and reactive nitrogen species (RNS) to an imbalance of skeletal muscle mechanism process. The soluble atrophy it's produced different oxidative stress state species such as O2 − , H2O2 and OH<sup>−</sup> . Where, it also needs antioxidant species state such as catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) and the last to imbalance denominated of oxidative stress, it's can produce oxidative damage in lipids, Deoxyribonucleic acid (DNA) and protein to impairing functional protein factor of cellular system [14].

Generation of ROS could uptake of oxygen, activation of NADPH oxidase and to production of the superoxide anion radical, see the reaction:

$$\text{2O}\_{2\*} \text{NADPH} \xrightarrow{\text{oxidence}} \text{2O}\_2^- + \text{NADP}^\* + \text{H}^\* \tag{1}$$

Where O2 − is converted to H2O2 (Eq. (2) by SOD

$$\text{2O}\_{2\*}\text{ 2H}^\* \xrightarrow{\text{SOD}} \text{H}\_2\text{O}\_2 + \text{O}\_2 \tag{2}$$

The skeletal of muscle atrophy could inactivity increase of mitochondrial reactive oxygen species (ROS) production on the ways. The mitochondrial could uptake of calcium and increase mitochondrial levels state of fatty acid hydroperoxides and the last depressed protein could transport into the mitochondria system. So, if the mechanism responsible, it's could increase mitochondrial fission [9].

The observation of muscle mass-specific overexpression of Peroxisome proliferator-activated receptor-y-coactivator-1α (PGC-1α) and the master regulator of mitochondria biogenesis could prevent activation of catabolic system and disuse of muscle atrophy system. The Peroxisome proliferator-activated receptory-coactivator-1α (PGC-1α) is mediated pathway and focuses on the role PGC-1α in the skeletal spinal muscular atrophy system by immobilization system. The Peroxisome proliferator-activated receptor-y-coactivator-1α (PGC-1α) is the master transcription stimulates of mitochondrial biogenesis pathway system with up the regulating system of the nuclear respiratory factors (NRF-1,2) and mitochondrial

*Background and Management of Muscular Atrophy*

spinal muscular atrophy is variable and depends on types of spinal muscular atrophy continuous spectrum with the age of death by infancy to normal life expectancy condition system on cell pathway system [6]. The Muscular atrophy its described with characterized generalized muscle and atrophy in the proximal limb muscle and phenotype by four grades of severity, where the spinal Muscular Atrophy I, spinal Muscular Atrophy II, spinal Muscular Atrophy III and spinal Muscular Atrophy IV, it's all depended by onset and motor spinal function [7, 8]. The muscular atrophy disease by the control mutation in the homozygous of survival motor neuron α (SMN 1) gene. The skeletal of muscular atrophy it's adverse consequences and the mechanism such as wasting or decrease of injury time. Lack of use in the spinal muscular atrophy and event disease category of spinal muscular atrophy. The spinal muscular atrophy it's usually considered by chronic diseases such as poliomyelitis,

Diabetes mellitus, cancer, renal failure or pulmonary obstruction [1].

ous redox-sensitive genes in spinal muscular atrophy disease [9].

and chronic inflammatory demyelinating polyneuropathy [13].

**3. Genetics of spinal muscular atrophy**

**2. Prevalence, incidence and carrier frequency of muscular atrophy**

According to the worldwide about a study into the prevalence and incidence of spinal muscular atrophy, where approximately 1–2 per 100.000 people and incidence around 1 in 10.000 live births have been estimated with the spinal muscular atrophy type I accounting for around 60% of all cases and estimation of the incidence of all types of spinal muscular atrophy of around 10 in 100.000 (1 in 10.000) live birth is cited [11]. Every incidence is a factor from a number of new cases of the disease in a particular time period. The evaluation of the incidence of all type SMA combined it's around 8 per 100.000 live births. The incidence of spinal muscular atrophy type I is around 4–6 in 100.000 and for the type II and III it's a high incidence combined 10,6 per 100.000 and for the gender, it's a nearly even split male and female [12]. The indicated difference of spinal muscular atrophy types is the between ethnicities and differences in health system clinically diagnosed. The prevalence in Indonesia of neuromuscular in RSCM hospital from January – December 2017 is 2,6% of all patients who come to the neurology outpatient ward. The five most who have neuromuscular disorders are neuropathy peripheral, Duchenne muscular dystrophy, spinal muscular atrophy, Guillain barre syndrome

Spinal muscular atrophy is a defect in survival motor neuron 1 (SMN 1) and it's gene localized to 5q11.2-q13.3). SMN gene (SMN 1 and SMN 2) on chromosome

To activation of spinal muscular atrophy, we need the process to activation of the distinct pathway (ATP) in proteolysis pathway. The condition of spinal muscular atrophy it's depends on the level of muscle protein nutrition system. To reduce the fiber muscle we need synthesis protein to innervate proximal hindlimb muscles and medical motor neurons axial muscles [9]. Mitochondrial is important in skeletal muscle to activation of function and subpopulation involved in cellular functions. Mitochondria play in role key on muscle fibers to the regulation of myonuclear apoptosis and serving uptake the calcium [10]. Mitochondria also continuously produce superoxide radicals and dismutated into hydrogen peroxide (H2O2), where H2O2 is a relatively and diffuse freely with cytosol, it's very important as signaling to the molecule on cell, to affecting multiple control of the cell cycle, uptake to cellular stress response, activation energy metabolism and also to the expression of numer-

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transcription factor A (Tfam) system, so it leads to increased mitochondrial DNA replication system and gene transcription system [15]. The Peroxisome proliferatoractivated receptor-y-coactivator-1α (PGC-1α) to appears key to the role-play a protective against of muscular atrophy linked skeletal muscle deterioration. The Peroxisome proliferator-activated receptor-y-coactivator-1α (PGC-1α) interacts with the nuclear receptors and activate transcription factors to activated their target gene. The activity to responsive multiple stimuli including calcium ion, Reactive oxygen species (ROS) and ATP demand pathway system on the cell system in the spinal muscular atrophy. The metabolic stress mediated by PGC-1α downregulation plays a major role in muscle atrophy and to adaptation the soleus to mice hindlimb unloading (HU) in the defuse, we need antioxidant treatment (Trolox). Which, the HU caused of reduction in the cross-sectional area, redox status alteration (NRF2, Superoxide dismutase1 and catalase up-regulation) and the autophagy (Beclin1 and P62 mRNA up-regulation) [16]. The attractive of PGC-1α states in muscle mass could restore and promote the muscle metabolic system when normal physical activity impossible. The observation of the muscle fiber – specific event until overexpression of the attractive of PGC-1α states, where a master regulator of the mitochondrial biogenesis, to prevent activation produce of the catabolic system and also disuse muscle atrophy.

#### **5. Antioxidant mechanism and function**

The natural antioxidant is one important to underlying to spinal muscular atrophy system. The natural antioxidant could effect to exercise the healthpromoting increase muscle defenses [17]. The natural antioxidant which role-plays to activation integrity on the cell and to prevent the free radical configuration tissue damage of muscle atrophy to normal healthy condition system of muscle atrophy pathway [18].

The natural antioxidant increasing antioxidative defenses and develop a synthesis of endogenous enzymes or increased antioxidant utilization, practice to maintain optimal body function to especially of spinal muscular atrophy in the redox condition on cell [19]. The function from natural antioxidant: it reduces the free radical of spinal muscular atrophy, stimulates the growth of normal cells, to protects the cell against the premature and abnormal aging condition of spinal muscular atrophy, helps fight the age-related molecular degeneration of spinal muscular atrophy and the last to supports the body immune system [17]. The natural antioxidant is powerful electron donors and also to the reaction of free radicals to target molecules breaking damaged on skeletal muscular. The lipid phase of chain-breaking antioxidant can scavenge the radicals in membranes and lipoprotein particles to preventing lipid peroxidation of skeletal muscular atrophy. The lipid phase such as tocopherols, ubiquinol, carotenoids and flavonoids and the aqueous phase such as ascorbate, urate, glutathione and other thiols [20, 21].

#### **6. Flavonoids are group of antioxidants**

Flavonoids are a group from based on natural substances by a variable phenolic structure, where are found from fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids are potential to anti-oxidative, anti-inflammatory and antimutagenic on spinal muscular atrophy disease [22]. As an anti-inflammatory, we need of agent system, where the COX is an endogenous enzyme with catalyzes function, which the conversion of arachidonic acid into prostaglandins and thromboxanes,

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*Total Antioxidant from Herbal Medicine as a Possible Tool for the Multifunctional Prevention…*

where the enzyme exists in two isoforms: COX - 1 is a constitutive enzyme and is responsible for the supply of prostaglandin and Cox – 2 is an inducible enzyme and is expressed an inflammatory stimulus and the stimulus prostaglandin to induction of inflammatory and pain. By using, the flavonoids can activate the molecular docking and knowledge bioinformatics in preventing chronic disease like as spinal muscular atrophy and to application and manufacturing in pharmaceutical medicinal industry [23]. Flavonoids subdivided of subgroup depending on the carbon of the C ring on which the B ring, which the degree of unsaturation and oxidation of the C ring. The firs isoflavone, which in the B ring is linked position 3 of the C ring. Second, the neoflavonoids, which the B ring is linked in position 4. Besides that, the subdivided into several subgroups on the basis which the B ring is linked position 2 on the basis of the structural features of the C ring. Flavonol (e.g. Quercetin, myricetin), flavone (eg. apigenin, luteolin), flavonolols (eg. taxifolin), flavan-3-ols (eg catechin, epigallocatechin), flavovone [24] (eg. hesperitin, naringenin), anthocyanidin (eg. cynidin,

*DOI: http://dx.doi.org/10.5772/intechopen.94184*

delphidin), isoflavone (eg. genistein, daidzein).

nins, steroid and glycosides [25].

**Compound Name**

1 Hyperoxide/ Hyperin

6 Coumarin scopoletin

**Table 1.**

**of** *Abelmoschus manihot*

**7.** *Abelmoschus manihot* **L. Medik is one of herbal medicine**

**8. Ethanomedicinal, phytochemical and pharmacological** 

*Some compounds isolated from the genus* Abelmoschus manihot *L. Medik [26].*

Ethanomedicinal, phytochemical and pharmacological profile of genus *Abelmoschus manihot* L. Medik where the genus *Abelmoschus manihot* L. Medik has been reported to used for several ethnomedicinal practices and also demonstrated diverse pharmacological activities and posses several phytochemical and nutritional properties as well as having and no adverse effect on living cells, their pods, seeds and leaves are reported to be used in pharmaceutical industries

*Abelmoschus manihot* L. Medik is have highest total antioxidant (**Table 1**). The leaf plant is a tropical plant from china, which is trapped by the name Huangkui. Ethanobotanical uses and phytochemical analysis of *Abelmoschus manihot* L. Medik, where the preliminary study shows the presence of alkaloid, carbohydrates, tan-

oxan-2-yl}oxy-4H-chromene-4,5,7-triol 2 Isoquercetin 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3{(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl} oxychromen-4-one

phenyl)5,7-dihydroxy-4H-1-benzopyran-4-one

alpha-L-mannopyranosyl)-beta-D-galactopyranosy} oxy)-2-(3,4-dihydroxyphenyl-4H-1-benzopyran-4-one

3 Myricetin 3,5,7-Trihydroxy-2-(3,4,5)-trihydroxyphenyl-4-chromenone 4 Hibifolin quercetin 3-beta-robinobioside; 3{(6–0-(6-Deoxy-alpha-L-

5 Quercetin 3-O-robinoside: Quercetin 3 –beta-robinobioside; 3-{(6-O-(Deoxy-

7-hydroxy-6-methoxychromen-2-one

Dihydroxyphenil)-3-{3R,4S,5R,6R)-3,4,5-trihydroxy-6(hydroxymethyl)

mannopryranosyl)-beta-D-galactopyranosyl}oxy)-2-(3,4-dihydroxy

#### *Total Antioxidant from Herbal Medicine as a Possible Tool for the Multifunctional Prevention… DOI: http://dx.doi.org/10.5772/intechopen.94184*

where the enzyme exists in two isoforms: COX - 1 is a constitutive enzyme and is responsible for the supply of prostaglandin and Cox – 2 is an inducible enzyme and is expressed an inflammatory stimulus and the stimulus prostaglandin to induction of inflammatory and pain. By using, the flavonoids can activate the molecular docking and knowledge bioinformatics in preventing chronic disease like as spinal muscular atrophy and to application and manufacturing in pharmaceutical medicinal industry [23]. Flavonoids subdivided of subgroup depending on the carbon of the C ring on which the B ring, which the degree of unsaturation and oxidation of the C ring. The firs isoflavone, which in the B ring is linked position 3 of the C ring. Second, the neoflavonoids, which the B ring is linked in position 4. Besides that, the subdivided into several subgroups on the basis which the B ring is linked position 2 on the basis of the structural features of the C ring. Flavonol (e.g. Quercetin, myricetin), flavone (eg. apigenin, luteolin), flavonolols (eg. taxifolin), flavan-3-ols (eg catechin, epigallocatechin), flavovone [24] (eg. hesperitin, naringenin), anthocyanidin (eg. cynidin, delphidin), isoflavone (eg. genistein, daidzein).
