|Year : 2020 | Volume
| Issue : 2 | Page : 37-44
An overview of Vatha Sura Kudineer (VSK): A potential Siddha antiviral drug
Shunmugaram Shenbagaraj, Lavanya Alagusolaiyan, Rajendra Kumar Arumugam
Siddha Regional Research Institute, Central Council for Research in Siddha, Puducherry, India
|Date of Submission||03-Mar-2022|
|Date of Acceptance||16-Mar-2022|
|Date of Web Publication||30-May-2022|
Dr. Shunmugaram Shenbagaraj
Siddha Regional Research Institute, Central Council for Research in Siddha, Puducherry 605013
Source of Support: None, Conflict of Interest: None
Introduction: The World Health Organization defines that communicable diseases are caused by microorganisms, fungi, insect bites, or contaminated water that can spread directly or indirectly, between persons. Chikungunya is an epidemic-prone vector-borne communicable disease caused by chikungunya virus (CHIKV). Due to the lack of appropriate treatment and vaccination, symptomatic or supportive treatments such as antipyretics, oral and tropical analgesics, and long-term anti-inflammatory therapy are the choices to manage chikungunya. This review aims to emphasize the potential role of a poly herbal Siddha formulation “Vatha Sura Kudineer (VSK)” used for the management of viral diseases in Siddha.
Materials and Methods: The scientific details including morphological description, phytochemical constituents, and their pharmacological studies along with Siddha perspectives were collected from books and published journals.
Results: This article provides comprehensive information of the ingredients of VSK, and it revealed their antiviral, antipyretic, anti-inflammatory, analgesic, antimicrobial, immunomodulatory, and antioxidant properties. Piperine and gingerol are the natural bioenhancers present in Piper longum Linn. and Zingiber officinale Roscoe, which may be enhancing the absorption and bioavailability of the formulation.
Conclusion: As there is a lack of effective antiviral and anti-inflammatory drugs for the treatment of Chikungunya, VSK would be a cost effective, potent drug which needs to be explored.
Keywords: Chikungunya, pharmacological studies, phytochemicals, Vatha Sura Kudineer, viral diseases
|How to cite this article:|
Shenbagaraj S, Alagusolaiyan L, Arumugam RK. An overview of Vatha Sura Kudineer (VSK): A potential Siddha antiviral drug. J Res Siddha Med 2020;3:37-44
|How to cite this URL:|
Shenbagaraj S, Alagusolaiyan L, Arumugam RK. An overview of Vatha Sura Kudineer (VSK): A potential Siddha antiviral drug. J Res Siddha Med [serial online] 2020 [cited 2022 Sep 29];3:37-44. Available from: http://www.jrsm.in/text.asp?2020/3/2/37/346337
| Introduction|| |
The World Health Organization defines communicable diseases are disorders that are caused by microorganisms, fungi, insect bites, or contaminated water that can spread directly or indirectly, between persons. Lower respiratory infections, neonatal disease conditions, and diarrheal disorders are some communicable diseases engaged in a major role in top 10 causes of death globally. Public health has enormous triumphs to control and eradicate some infectious diseases by many initiatives and programs. Vaccines and antibiotics are such important inventions that brought a sense of optimism to public health, which make people to believe that infectious diseases could be controlled. In India, small pox, guinea worm, and poliomyelitis have been eradicated due to the strenuous programs led by the Government. The Universal Immunization Program was initiated by the GoI in 1989–1990 for the welfare of infants, children, and pregnant women to reduce the prevalence of communicable diseases.
Chikungunya is a vector-borne epidemic disease caused by chikungunya virus (CHIKV), which made a breakout in India in the year of 2006 and affected nearly 1.38 million population. Mourya et al. mentioned 4% of people are affected with chikungunya based on disease-wise viral outbreaks reported in India. Low-to-high grade fever is one of the commonest clinical features that occur in 92% of the infected people, lasting for 24–48 h. Viral infection enhanced the formation of proinflammatory mediators (cytokines such as interleukin (IL)-1β, α, β and tumor necrosis factor-alpha (TNF-α)), which increase the synthesis of prostaglandin E2 (PGE2) near peptic hypothalamus area, leading to elevation of body temperature. Ankles, wrists, knees, shoulders, and spine are the major joints involved in arthralgia associated with fever, and it was reported in 87% of the cases.
Pain is a complex inflammatory process mediated via prostaglandins, bradykinins, and substance-P like physiological mediators. The arthralgia of lower limbs led to disability resulting in a slow and broad halting gait, which was persisting for months. The disease has high morbidity rate of polyarthritis leading to considerable disability and it caused substantial socioeconomic impact in affected countries.,, Symptomatic or supportive treatments such as antipyretics, oral and tropical analgesics, and long-term anti-inflammatory therapy are the choices to manage chikungunya, due to the unavailability of vaccine. About 25% of chronic non-steroidal anti-inflammatory drug (NSAID) users will develop upper gastrointestinal tract injury, and 2–4% will bleed or perforate. Concerns rise due to potential cardiovascular risk of COX-2 inhibitors and other NSAIDs. Fever with rigor, arthralgia of major and minor joints associated with swelling, stiffness and restricted movements of joints, anorexia, indigestion, constipation, sleeplessness, and black discoloration of skin are the major signs and symptoms of Vatha Suram that can be correlated with chikungunya.,,
Followed by the major outbreak of chikungunya in 2006, the Department of AYUSH studied the effect of Siddha medicines on chikungunya patients and recommended specific regimen for the management. Nilavembu Kudineer (NVK) played a vital role to control the epidemic outbreak and manage the clinical features of chikungunya. Antiviral, antipyretic, anti-inflammatory, analgesic, antioxidant, and anti-atherogenic activities of NVK have been exhibited against CHIK virus.,, Apart from this, abundant Siddha formulations are exclusively mentioned for Vatha Suram. Vatha Sura Kudineer (VSK) is one such classical polyherbal formulation mentioned in Theraiyar Kudineer widely used and prescribed as a single or additional medicine among Siddha Physicians. Hence, this study aims to review the efficacy of ingredients in VSK against CHIK virus by using pharmacognostical aspect and phytopharmacological scientific studies. The Siddha pharmacological aspect of VSK in relation to Vatha Suram is also elucidated.
| Ingredients And Standard Operating Procedure Of Vatha Sura Kudineer|| |
Kandankathiri Vaer (Solanum surattense Burm.)
Siruthekku (Clerodendrum serratum Linn.)
Korai Kizhangu (Cyperus rotundus Linn.)
Sukku (Zingiber officinale Roscoe)
Thippili moolam (Piper longum Linn.)
Take equal amount of the above ingredients and make it into a coarse powder. Then 3 L of water is added to the ingredients and boiled to reduce up to 1/8th of the added water and filtered. It can be consumed with the dosage of 30–60 mL, twice in a day.
| Vatha Sura Kudineer: Pharmcognostic Aspect|| |
Kandankathiri Vaer (S. surattense Burm.)
S. surattense is a prickly, diffused perennial herb, about 1.2 m tall usually with a woody base. The root is 10–45 cm long, almost cylindrical and tapering, bearing a number of fine longitudinal and few transverse wrinkles with lenticels, small rootlets, and bitter in taste.
These include solasodine, solamargine, β-solamargine, solasonine, cycloartenol, neocarpesterol, cholesterol, and their derivatives.
Siruthekku (C. serratum Linn.)
It is a perennial shrub, stem scarcely woody not much branched native to East India and Malaysia, up to 3–8 feet in height with blunt quadrangular stems and young parts are usually glabrous. Mature root hard, woody, cylindrical; up to 5 cm thick; external surface light brown having elongated lenticels.
Preliminary studies of C. serratum root reported the presence of flavonoids, glycosides, saponins, and sterols. In another screening, the root showed the presence of alkaloids and saponins and the absence of tannins. The root bark contained D-mannitol, glucose, and saponins.
Korai Kizhangu (Cyperus rotundus Linn.)
It is a perennial plant that may reach a height of up to 40 cm also called as “nut grass” due to the rhizome resembling nuts. The root system of a young plant initially forms white, fleshy rhizomes. Some rhizomes grow upward in the soil and then form a bulb-like structure from which new roots and rhizomes grow. Other rhizomes grow horizontally or downward and form dark reddish-brown tubers or chains of tubers.
The rhizome of Cyperus rotundus is rich in active constituents such as sesquiterpenoids, patchoulenone, sugetriol triacetate and sugebiol, sugeonyl acetate, isopatchoulenone, cyprot-3-en-2-one-14-oic acid, aliphatic ketones, fatty esters, steroidal esters, β-sitosterol-3, β-O-glucoside, and lupenyl 3β-O-arabinpyranosyl oleate as well as flavonoids such as kaempferol, luteolin, and quercetin.,
Sukku (Z. officinale Roscoe.)
It is a perennial rhizomatous herb with irregularly branched rhizomes which are white to yellowish brown in color. Rhizome has smooth surface and fibrous elements; longitudinal striations are present in the cut if it is broken. The broken pieces are nearly 5–15 cm long, 1–1.5 cm wide, and 1–1.5 cm thick. The rhizome has an agreeable aromatic odor and pungent taste.
Ginger is rich in active constituents, such as phenolic and terpene compounds. Gingerols (6-gingerol, 8-gingerol, and 10-gingerol), shogaols, paradols, quercetin, zingerone, gingerenone-A, and 6-dehydrogingerdione are main phenolic compounds present in ginger. Curcumene, zingiberene, farnesene, bisabolene, and sesquiphellandrene, which are considered terpene compounds, present ginger essential oils. Polysaccharides, lipids, organic acids, and fibers are also present in ginger.
Thippili moolam (P. longum Linn.)
It is a slender, aromatic, climber with perennial woody roots, creeping and jointed stems, and fleshy fruits embedded in the spikes. The roots are transversely cut pieces 5–25 mm long and 2–7 mm diameter, which is cylindrical, straight, or slightly curved. The roots have distinct, swollen internodes exhibiting a number of leaf and rootlet scars in a dirty light brown color. It has a peculiar odor and a pungent bitter taste that produces numbness on the tongue.,
The cold ethanol extract of P. longum roots consists of cepharadione B, cepharadione A, cepharanone B, aristolactam A II, Norcepharadione B, 2-hydroxy-1-methoxy-4H-dibenzo, quinoline-4, 5(6H)-dione, 10-amino-4-hydroxy-3-methoxyphenanthrene-1-carboxylic acid lactam [piperolactam A], 10-amino-4-hydroxy-2, 3-dimethoxyphenanthrene-1-carboxylic acid lactam [piperolactam B], pluriatilol, fargosin, sesamine, asarinine, guineensine, and pipercide.
| Pharmacological Review Of VSK|| |
Kandankathiri Vaer (S. surattense Burm.)
Anti-inflammatory, analgesic, and antipyretic activities
The in-vivo evaluation of anti-inflammatory, antipyretic, and analgesic activity of solasodine transdermal patches (TDS) was carried out in rats by carrageenan-induced paw edema test, Brewer’s yeast-induced pyrexia method, and acetic acid-induced writhing experiment, respectively. The TDS exhibited better anti-inflammatory (57.1%), analgesic (26.1%), and anti-pyretic activity (4.2%) when compared with standard indomethacin and aspirin.
Pardhi et al. evaluated the antimicrobial activity of extracts of S. xanthocaroum tested under in-vitro conditions by agar well diffusion method against three bacterial and one fungal pathogens. The aqueous, hydroethanolic, and ethanolic extract of S. xanthocarpum (50 μg/mL) inhibited the growth of Gram-negative bacteria Staphylococcus aureus (10, 15, and 13 mm, respectively) and Escherichia coli (6, 8, and 7 mm, respectively). The ethanolic extract was found to be having more potent antimicrobial activity than that of aqueous and hydroethanolic extract.
The antioxidant activity of S. xanthocarpum was assessed using ferric reducing antioxidant power and reducing power scavenging assays. The FRAP assay evaluates the ability of a substance to reduce Fe3+ to Fe2+, which is measured by the formation of a colored complex with tripyridyltriazine that can be read spectrophotometrically at 593 nm. Since the antioxidant activity of a substance is usually correlated to its reducing capacity, this assay provides a reliable method to evaluate the antioxidant activity. The hydroethanolic extract of the herb was found to be having antioxidant activity.
Siruthekku (C. serratum Linn.)
Narayanan et al. evaluated the antipyretic activity by administration of C. serratum orally in doses of 50, 100, and 200 mg/kg, 60 min after TAB vaccine-induced pyrexia. Paracetamol 100 mg/kg was used as a comparator. The reduction of pyrexia was significant with 100 and 200 mg/kg doses.
The methanolic extract of C. serratum L. roots on carrageenan-induced paw inflammation at doses of 200 and 400 mg/kg has significant inhibition against cyclooxygenase and prostaglandin synthesis. Pretreatment with C. serratum L. has inhibited the carrageenan-induced paw edema at +1, +2, +3, +4, and +5 h, respectively.
The ethanol extract of roots of C. serratum has been screened for their antibacterial activity. The extract (7.5 mg/disc) showed broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. The results were compared with the standard drug streptomycin (10 μg/disc). The zone inhibition was found to be increased with the increase in concentration of the extract, thus exhibiting concentration-dependent activity.
The immunomodulatory activity of the aqueous extract of C. serratum roots (100 and 200 mg/kg, p.o.) was through phagocytic and proliferation assays in mice peritoneal macrophages. The extract was tested for hemagglutinating antibody titer (HAT) and delayed-type hypersensitivity (DTH) reactions in mice (in vivo, 14 days, ovalbumin). The results showed an improvement of innate immunity attributed to the ability to stimulate both adaptive and innate immune responses either through stimulation of macrophages or through stimulated release of factors involved in the proliferation of bone marrow cells in mice.
The results of the present study show that the ethanolic extract of the roots of C. serratum possesses antioxidant activity through the DPPH free radical scavenging activity, reducing power assay, and scavenging of hydrogen peroxide. The preliminary phytochemical investigation indicates the presence of flavonoids in the plant. Polyphenols such as flavonoids and tannins are the well-known natural antioxidants.
Korai Kizhangu (Cyperus rotundus Linn.)
The alcoholic extract of Cyperus rotundus L. showed highly significant antipyretic activity against pyrexia induced in albino rats by the subcutaneous injection of suspension of dried Brewer’s yeast in gum acacia in normal saline. However, a specific fraction obtained from the petroleum ether extract showed significant antipyretic effect similar to acetyl salicylic acid.,
Anti-inflammatory, antiarthritic, and analgesic activity
Biradar et al. evaluated the anti‐inflammatory, antiarthritic, and analgesic activities of Cyperus rotundus L. essential oils using carrageenan-induced, formaldehyde-induced, and formalin-induced writhing in rats, respectively. Pretreatment with Cyperus rotundus L. at doses of 250 and 500 mg/kg reduced the paw edema from 2nd hour after carrageenan injection when compared with controls. Pretreatment with Cyperus rotundus L. at doses of 250 and 500 mg/kg showed a dose-dependent effect. On 10th day, treatment with Cyperus rotundus L. (500 mg/kg) reduced the swelling up to 75.54% in the injected (left) hind paw when compared with treatment with diclofenac sodium. Analgesic effects on neurogenic and inflammatory pains were evaluated on both first (0–5 min) and second (15–30 min) phases of formalin-induced pain. Essential oil inhibited both pains at a dose of 500 mg/kg, which significantly blocked the inflammatory pain.
Imam and Sumi evaluated anti-nociceptive activity of Cyperus rotundus L. by the hot-plate tail-immersion test and formalin-induced paw licking test in mice at three different doses (50, 100, and 200 mg/kg). Morphine sulfate (5 mg/kg, i.p.) and diclofenac sodium (10 mg/kg, i.p.) were used as controls. All the tested doses (50, 100, and 200 mg/kg) significantly increased the latency period to the thermal stimuli and decreased the licking of paw in late phase. The dose 200 mg/kg was most effective showing a maximum percentage of inhibition of licking in both early (61.60%) and late phases (87.41%).
Antimicrobial activity of aqueous, ethyl acetate, methanolic, and TOF extracts of Cyperus rotundus L. was evaluated using disc diffusion against Gram-positive bacteria such as Staphylococcus aureus and Enterococcus faecalis and Gram-negative bacteria such as E. coli, Salmonella enteritidis, and Salmonella typhimurium.
In-vitro antioxidant and free radical scavenging activities of 70% ethanolic, methanolic, and water extracts of Cyperus rotundus L. root exhibit the most potent IC50 values of 64.64 ± 5.3 g/mL, 85.89 ± 6.3 g/mL, and 8.42 ± 0.45 mg/mL against DPPH, metal chelating, and nitric oxide scavenging activities in 70% ethanolic extract. The extract of Cyperus rotundus L. showed 48% protection against H2O2-induced DNA damage and inhibited the AAPH- and SIN-1-induced oxidation and nitration of bovine serum albumin. Cyperus rotundus showed acetylcholine esterase inhibitory activity, and the extract was found to be non-toxic up to 100 g/mL in SH-SY5Y human neuroblastoma cell line.
The ethanol extract of Cyperus rotundus was able to normalize the population of lymphocyte T cells and suppressed CD4 and CD8 cells in a dose-dependent manner. Sixty female BALB/c mice were injected with 7,12-dimethylbenz[a]anthracene subcutaneously, and the Cyperus rotundus extract was administered orally in three different doses at 31.68, 158.4, and 316.8 mg/kg. The extract suppressed the levels of TNF-α, IFN-γ, IL-1β, and IL-6 expressed by macrophages.
Sukku (Z. officinale Roscoe)
Kaushik et al. evaluated the in-vitro antiviral effect of Z. officinale against Chikungunya virus. They exhibit that the maximum non-toxic dose assay of aquatic extract of the fresh rhizome in the Vero cell line was 62.5 μg/mL. They also calculated the tissue culture infective dose at a level of 103 TCID50/mL for antiviral assay. Chang et al. evaluated the antiviral effect of fresh ginger against Human Respiratory Syncytial Virus infection in human respiratory tract cell lines. High concentration of Z. officinale could stimulate mucosal cells to secrete IFN-β, which is responsible in counteracting viral infections by reducing viral attachment and internalization. The calculated IC50 of fresh rhizome was 144.9 mg/mL in HEp-2 cells and 73.3 mg/mL in A549 cells.
Mascolo et al. revealed the antipyretic effect of Soxhlet extract of ginger in 80% ethanol and reduced yeast-induced fever in rats by 38% when administered orally (100 mg/kg). Acetylsalicylic acid at the same dose is used to compare the effect. The ginger extract did not affect the temperature of normothermic rats.
Anti-inflammatory and analgesic activities
Zehsaz et al. evaluated the effect of Z. officinale on proinflammatory cytokine levels in athletes by the administration of ginger for 6 weeks. They also stated that the usage of ginger possibly reduces the chances of infection and potentially reduces the cytokine inducing fatigue. The in-vivo anti-inflammatory effect of an aqueous ginger extract is assessed by carrageenan-induced paw edema in rats. Results showed that the extract caused a significant dose-dependent decrease in the production of PGE2, TNF-α, IL-6, and the monocyte chemoattractant protein-1 (MCP-1), suggesting that the anti-inflammatory effect was due to inhibition of macrophages and neutrophils activation and leukocytes migration.
The ethanol extracts and crude flavonoids of Z. officianale rhizome exhibit antibacterial activities against E. coli, Staphylococcus aureus, Shigella fiexneri, Proteus vulgaris, and Pseudomonas aeruginosa. Atai et al. exhibited the antifungal activity of the ethanol extract of Z. officinale two strains of Candida albicans.
The essential oils of Z. officinale were evaluated for immunomodulatory activity, using rats as the animal model in foot pad thickness response. The essential oils were tested for HAT and DTH, using sheep red blood cells (SRBCs) as the antigen whereas sodium carboxymethyl cellulose (SCMC) as control. Hemagglutination titer of geraniol showed the highest increase of 139.3 ± 6.38 and 5.9 ± 0.7 DTH, respectively. The essential oils have a noteworthy immunostimulant activity on specific and non-specific immune mechanisms.
Hosseinzadeh et al. evaluated the antioxidant activity of Z. officinale in C28I2 human chondrocyte viability by methylthiotetrazole assay. Ginger extract treatment reduced IL-1β-induced elevation of ROS, lipid peroxidation, the Bax/Bcl-2 ratio, caspase-3 activation and increased the gene expressions of antioxidant enzymes. The results exhibit the antioxidant properties of ginger by leading to a reduction in oxidative stress.
Thippili moolam (P. longum Linn.)
Teotino et al. evaluated the antipyretic activity in rats by inducing subcutaneous injection of 1 mL/100 g body weight of 25% yeast in NSS. The test substance P. longum L. extract (300, 600, 1200 mg/kg), aspirin (300 mg/kg), and 5% Tween-80 (control group) were orally administered. The P. longum L. extract in variable doses possesses significant action to reduce the rectal temperature of rats.
Sharma evaluated the antiviral activity of P. longum against ribosomal inactivating proteins (RIP) by inhibiting the proteins in viral infections.
Khan and Siddiqui tested extracts of P. longum L. against Staphylococcus albus, Salmonella typhi, P. aeruginosa, E. coli, Bacillus megaterium, and Aspergillus niger. The effective action of P. longum extract against these bacterial strains was attributed due to the alkaloids and terpenoids present in crude drug.
Immunoregulatory potential of P. longum in Balb/C mice (in vivo) exhibited dose-dependent (10, 20, 40, and 80 mg/kg p.o.) decrease of lymphocytes (CD4 + and CD8+T-cells) and cytokine levels in sensitized Balb/C mice with a marked inhibition at 40 mg/kg. At doses of 20 and 5 μg/mL, P. longum exhibited significant inhibition of mitogen-induced human PBMC proliferation, mRNA transcripts of IL-2 (Con A) and TNFα, IL-1β, and iNOS (LPS) in human PBMC models under stimulated conditions in time-dependent (6, 12, and 24 h, respectively) expression studies.
Vedhanayaki et al. evaluated the analgesic activity of P. longum L. root using rat tail-flick method and acetic-acid writhing method by opioid-type analgesics, pentazocine (i.p.), and ibuprofen (oral) as respective control drugs. Both ibuprofen (40 mg/kg) and P. longum (800 mg/kg) showed 50% protection against writhing. The 400 and 800 mg/kg doses of P. longum exhibited significant NSAID type of analgesia.
Dhargawe et al. studied carrageenan-induced paw edema for acute inflammation. The percentage of inhibition at 3 h was 61.57% for the aspirin group and 55.81% for the piperine group when compared with the control group. According to Stöhr et al., the Piper extracts and piperine possess inhibitory activities on prostaglandin and leukotrienes COX-1 inhibitory effect and thus exhibit anti-inflammatory activity.
| Siddha Medicine Concepts About Vatha Sura Kudineer|| |
| Conclusion|| |
The scientific studies explored the ingredients of VSK that predominantly possess antiviral, antipyretic, anti-inflammatory, analgesic, antimicrobial, immunomodulatory, and antioxidant activities  . They also moderately possess anti-nociceptive, hepatoprotective and nephroprotective activities.,,,,,,,,,,,,,,,,,,,,, Kaushik et al. evaluated the in-vitro antiviral effect of Z. officinale against Chikungunya virus. Piperine and gingerol are the natural bioenhancers present in P. longum and Z. officinale, which may be enhancing the absorption and bioavailability of the formulation. The toxicity studies of the ingredients revealed that the drugs are safe for human administration., ,,, This scientific evidence substantiated the therapeutic uses of herbs stated in the classical Siddha literatures, as given in [Table 1]. As per Siddha, the ingredients of VSK predominantly consist of pungent (Kaarpu) followed by astringent (Thuvarppu) and bitter (Kaippu) taste. Thus, it alleviates the vitiated vatham humor responsible for the clinical symptoms such as fever with rigor, arthralgia with swelling, stiffness, anorexia, indigestion, constipation, and sleeplessness through their anti-vatha mechanism. From the literatures reviewed, the therapeutic indications mentioned for the VSK may be due to its synergetic effect than due to its individual herbs. Thus this review supported the traditional claim of VSK and we postulated that this classical formulation has an effect to treat Chikungunya. This review may create an initiation to conduct various preclinical and clinical studies in VSK to validate its clinical efficacy. As there is a lack of effective antiviral and anti-inflammatory drugs for the treatment of Chikungunya, VSK would be a cost-effective, potent drug, which needs to be explored.
|Table 1: Ingredients of VSK with the taste of each drug, parts used, and actions of the drug|
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