Kupilu (Strychnos Nux Vomica)

Recent Research on Kupilu

• The present study aimed to evaluate the various pharmacognostic characters and antidiabetic activity of the S. nux-vomica seed. S. nux vomica extracts show antihyperglycemic activity in experimental animals. Bhati R, Singh A, Saharan VA, Ram V, Bhandari A. Strychnos nux vomica seeds: Pharmacognostical standardization, extraction, and antidiabetic activity. J.  Ayurveda Integr Med. 2012 Apr; 3 (2): 80- 4, dot: 10. 4103/ 0975- 9476. 96523.
• This study was carried out to investigate the effect of removing most strychnine from the total alkaloid fraction (TAF) extracted from nux vomica on analgesic and anti-inflammatory activity and pharmacokinetics after transdermal administration. The results from the present study appeared to support the viewpoint that most strychnine should be removed from TAF to improve analgesic and anti-inflammatory activity. Chen J, Wang X, QuYG, Chen ZP, Cai H, Liu X, Xu F, Lu TL, Cai BC. Analgesic and antiinflammatory activity and Pharmacokinetics of alkaloids from seeds of Strychnos nux-vomica after transdermal administration: effect of changes in alkaloid composition. J Ethnopharmacol. 2012 Jan 6; 139 (1): 181- 8. doi: 10. 1016/ j. jep. 2011. 10. 038. Epub 2011 Nov 10.
• In the present study, they examined its possible immunomodulatory effect on the induction of ovalbumin (OVA)-specific IgE antibody response in a murine model, as evaluated by passive cutaneous anaphylaxis (PCA). The results confirm the suppressive activity of S. nux-vomica on allergen-specific IgE antibody response and suggest its possible application in allergic conditions. Duddukuri GR, Brahmam AN, Rao DN. Suppressive effect of strychnos nux-vomica on induction of ovalbumin-specific IgE antibody response in mice. Indian J. Biochem Biophys. 2008 Oct; 45 (5): 341- 4.
• In the present study, the powder of raw and processed Kupeelu seeds (processed/purified with Kanji i.e., sour gruel) as test drugs were assessed for anti-inflammatory activity by employing Carrageenan and Formaldehyde induced hind paw edema in Wistar strain albino rats at a dose of 22.5 mg/kg body weight orally. This study reveals that both raw and purified Kupeelu showed the presence of highly significant anti-inflammatory activity against formaldehyde-induced hind paw edema but did not have similar activity against Carrageenan-induced hind paw edema. Mitra S, Kumar V, Ashok B, A, Acharya RN, Ravishankar B. Comparative anti-inflammatory activity of raw and processed Kupeelu (Strychnos nux-vomica Linn.) seeds on albino rats. Anc Sci Life. 2011 Oct; 31 (2): 73- 5.
• Strychnine showed remarkable negative chronotropic activity on frog-isolated hearts and guinea pig atria (J. Pharm. Pharmacol. 1970, 22, 380). (2) Strychnine (50 mg/kg S.C.) increased the level of acetylcholine in the spinal cord and sustained convulsions in frog hearts (Brit. J. Pharmacol, 1972, 45, 173).
• Lee, Jeung-Min & Park, Jae Hee & Park, Hae-Ryong & Park, Eun-Ju. (2010). Antioxidant and Alpha-Glucosidase Inhibitory Activity of Strychnos nux-vomica Extracts. Journal of the Korean Society of Food Science and Nutrition. 39. 1243-1248. 10. 3746/ jkfn. 2010. 39. 9. 1243. The physiological activities of Strychnos nux-vomica extracts were investigated through the total phenolic contents (TPC), 1,1- diphenyl- 2- picrylhydrazyl (DPPH) radical scavenging activity (RSA), comet assay, and α- glucosidase inhibitory activity. S. nux-vomica extracts were prepared with methanol, ethanol, and acetone. The methanol extract showed the highest phenolic content (71 mg/ 100 g gallic acid equivalents). Pretreatment with S. nux-vomica extracts resulted in significant reductions in oxidative DNA damage at all of the concentrations tested (1& 50 μg/ mL). The α-glucosidase inhibitory activity of a methanol extract was 12.8 % at the concentration of 1 mg/ mL. Therefore, these results indicate that S. nux- vomica might be a noble potential candidate exhibiting antioxidant and α- glucosidase inhibitory activity. 
• Strychnine (1.0 to 100.0 um) inhibited nicotinic stimulation of catecholamine release from bovine-cultured adrenal chromaffin cells in a concentration-dependent manner, it also inhibited nicotine-induced membrane depolarization and increase intracellular 2+ Ca concentration. Results suggest that strychnine interacts with the agonist binding site of nicotinic acetylcholine receptors in chromaffin cells, thus exerting a pharmacological effect independent of the glycine receptor (Brit. J. Pharmacol. 1994, 113, 471).
• Chaurasia, Savita. (2009). Anti-inflammatory and Antioxidant Activity of Strychnos nux vomica Linn. American-Eurasian Journal of Sustainable Agriculture. 3. 244- 252. Strychnos nux-vomica Linn. (Loganiaceae) is an evergreen tree native to Southeast Asia. In traditional medicinal systems seeds, bark and leaves have been used in a variety of diseases. Seeds are widely used in the treatment of Eczema, rheumatism, paralysis, asthma, diabetes, piles, etc. In the present study, the Anti-inflammatory and Antioxidant activities of the alcohol extract of the Strychnos nux vomica were assayed in Charles Foster albino rats. Acute and chronic inflammation models were used to evaluate the anti-inflammatory activity (in vivo). In the acute model, carrageenan was used to induce inflammation in the rat’s hind paw, and the cotton pellet-induced granuloma method was used for the chronic inflammation model. The antioxidant property was assessed on enzymatic and non-enzymatic models of lipid peroxidation induced by Fe3+- ADP (1.6 mM-  62 μM) and FeSO4 (0.5  mM) respectively (in vitro). The degree of lipid peroxidation was measured by TBARS estimation. Leve l of reduced glutathione (GSH) was estimated by the method of Ellman (1959). To evaluate the antihepatotoxic activity of S. nux vomica extract level of serum transaminases (SGOT and SGPT) was measured by the method of Reitman and Franke l (1957). The extract (50–200 mg/ kg-1 b.w., p.o.) exhibited dose and time-dependent significant inhibition on both the models of inflammation. At a dose of 200 mg/ kg-1 b.w. for 7,15 and 30 days 40%, 72%, and 95% inhibition in edema formation (acute model) was found respectively. In the chronic model at a dose of 200 mg/ kg-1 b.w. for 7 and 21 days there was 24.75% and 58% inhibition in cotton pellet granuloma respectively. The extract also inhibited both models of lipid peroxidation in a dose-dependent manner. ED50 was found to be 149μg /ml and 85μg/ml on FeSO4 and Fe -ADP models of lipid 3+ peroxidation respectively. It significantly inhibited aerobic as well as FeSO4-induced depletion of GSH in a time and dose-dependent manner. Oral treatment of drugs up to 200 mg kg -1 b.w. for 30 days did not show any rise in serum transaminases (SGOT and SGPT). The results obtained in this study indicated that the ethanol extract of Strychnos nux vomica possesses potent anti-inflammatory and antioxidant properties with no detectable adverse effects. These results confirm the use of S. nux vomica traditionally for the treatment of rheumatism and other inflammatory conditions.
• Deng, Xu-Kun & Yin, Wu & Li, Wei- Dong & Yin, Fang- Fang & Lu, Xiao-Yu & Zhang, Xiao-Chun & Hua, Zi- Chun & Cai, Bao- Chang. (2006). The anti-tumor effects of alkaloids from the seeds of Strychnos nux- vomica on Hep G2 cells and its possible mechanism. Journal of Ethnopharmacology. 106. 179- 86. 10. 1016/ j. jep. 2005. 12. 021. To screen the anti-tumor effects of the four alkaloids: brucine, strychnine, brucine N-oxide, and iso-strychnine from the seed of Strychnos nux-vomica, MTT assay was used to examine the growth inhibitory effects of these alkaloids on human hepatoma cell line (HepG2). Brucine, strychnine, and iso-strychnine revealed significant inhibitory effects against HepG2 cell proliferation, whereas brucine N-oxide didn’t have such an effect. In addition, brucine caused HepG2 cell shrinkage, membrane blebbing, and apoptotic body formation, all of which are typical characteristics of apoptotic programmed cell death. The results of flow cytometric analysis demonstrated that brucine caused dose-dependent apoptosis of Hep G2 cells through cell cycle arrest at G0/G1 phase, thus preventing cells from entering S or G2/ M phase. Immunoblot results revealed that brucine significantly decreased the protein expression level of cyclooxygenase-2, whereas increased the expression of caspase-3 as well as the caspase-3-like protease activity in Hep G2 cells, suggesting the involvement of cyclooxygenase- 2 and caspase- 3 in the pro-apoptotic effects exerted by brucine. Therefore, this paper indicates that the major alkaloids present in the seed of Strychnos nux-vomica are effective against Hep G2 cells proliferation, among which brucine proceed HepG 2 cells death via apoptosis, probably through the participation of caspase- 3 and cyclooxygenase- 2.
• Tripathi, Yamini Bhusan & Chaurasia, Savita. (1996). Effect of Strychnos nux vomica alcohol extract on lipid peroxidation in rat liver. Pharmaceutical Biology – PHARM BIOL. 34. 295- 299. 10. 1076/ phbi. 34. 4. 295. 13222. This report investigates the antioxidant properties of the purified Strychnos nux vomica L. seed extract for protection against the non-enzymatic formation of lipid peroxides and reduced glutathione (GSH) levels in rat liver homogenate. Results were compared with the natural antioxidant vitamin E. For the first time, it could be reported that this drug protects against cumene hydroperoxide (CHP) induced lipid peroxidation in a dose-dependent manner. It also inhibits the process of lipid peroxidation, once induced. The drug significantly maintains the hepatic content of glutathione in a dose and time-dependent manner, even in the presence of the above toxin (CHP). Thus it appears that S. nux vomica is a potent antioxidant and the mechanism of action could be through the scavenging of free radicals.
• Joy, A. & Appavoo, M. (2015). Antibacterial and antifungal activity of Strychnos nux vomica seed extract. 7. 1495- 1499. The antimicrobial activity of the ethanolic extract of Strychnos nux vomica seeds was studied. The invitro antimicrobial activity was performed by the agar disc diffusion method. The most susceptible bacteria gram-positive bacteria identified were Staphylococcus aureus and gram-negative bacteria were Escherichia coli and Klebsiella pneumoniae. All the fungal species showed resistance to the extract. The effects of the extract on these microbes were compared against the standard antibiotics such as ampicillin and amphotericin with 20 μg/ disc. In this study, Strychnos nux vomica seed extracts showed maximum inhibition against the gram-negative bacteria and less or no inhibition against the fungal organisms tested. From this study it was identified that ethanolic seed extracts of this tree could be used to control the above said microbes.
• Mahesh, Glad & Joy, A & Ratchagan, K & Sundaramurthy, A. (2015). Antibacterial and antioxidant activity of Strychnos nux vomica flower extract. Journal of Chemical and Pharmaceutical Research. 2015. 748- 752. This study aimed to investigate the antibacterial and antioxidant activity of the methanolic extract of Strychnos nux vomica flowers. Results showed that the plant was able to inhibit all the microorganisms chosen however its effect was higher with Candida albicans and Klebsiella pneumoniae with Chloramphenicol (10 ug/ ml) as the standard drug of choice. The samples were evaluated for their radical scavenging activity against the synthetic DPPH (2, 2- diphenyl- 1- picryl- hydrazine), and the results showed high antioxidant activity. Further, this study showed that the flowers of this plant can be used to treat infections caused by these tested microorganisms. More research is needed to isolate the active compounds and determine the structural composition and their mode of action in inhibiting these bacteria.
• Khan, Merajuddin & Garg, Ankur & Srivastava, Santosh & Darokar, Mahendra. (2012). A cytotoxic agent from Strychnos nux-vomica and biological evaluation of its modified analogs. Medicinal Chemistry Research. 21. 2975- 2980. 10. 1007/ s00044- 011- 9832- 9. Although several chemicals have been isolated from Strychnos nux-vomica, only a few have been evaluated for their biological significance. As a part of our drug discovery program for cytotoxic agents from Indian medicinal plants, a novel cytotoxic agent, loganin 1 was isolated from the fruit pulp of S. nux-vomica. The loganin 1 showed significant anticancer activity against the human liver (WRL- 68), colon (COLO- 320 and CaCo2), ovarian (PA- 1), and breast (MCF- 7) cancer cell lines. Loganin 1 was further chemically transformed into eleven semi-synthetic derivatives 2–12 of which 20, 30, 40,  7-tetra- Oacetyl- 60- O- (3000, 4000, 5000)- tri methoxy benzoyl loganin 11 and 20,30,40,7-tetra-O-acetyl-60-O-lauroyl loganin 6 derivatives showed eight, 13 and three times while 20,30,40,7- tetra-O-acetyl-60-O-lauroyl loganin 6 showed equal, 13 and two times more activity against human suspension colon (CaCo2), adherent colon (COLO- 320) and liver (WRL- 68) cancer cell lines, respectively than the known anticancer agent, vinblastine. The other analogs (except 4, 8, and 9) and loganin also showed marginal to moderate anticancer activity against the five tested human cancer cell lines.
• Sv, Gopalkrishna & Narasu, M. & Siddamsetty, Ramachandra Setty. (2010). Hepatoprotective activity of detoxified seeds of nux-vomica against CCl4 induced hepatic injury in albino rats. Pharmacologyonline. 1. 803- 815. The present study was conducted to assess the effect of detoxification (shodhana) on the phytochemical, hepatoprotective, and tissue antioxidant activity of seeds of Strychnos nux-vomica L. The seeds were subjected to the shodhana process as prescribed in ancient texts of Ayurveda and a native Ayurvedic practitioner with slight modification. In the ancient process, the seeds were detoxified by immersing seeds in cow’s urine for 7 nights, then Sweden (boiled with cow’s milk for 3 hours) and finally fried with cow’s ghee. In the 2nd process instead of swedana, the seeds were immersed in cow’s milk for 3 days, and the remaining procedure was described as per ancient literature. Three samples (unprocessed and processed by two procedures were subjected to screen for phytochemical and hepatoprotective properties. CCl4-induced hepatotoxicity in rats was used as an animal model and biochemical parameters like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), serum bilirubin, serum cholesterol and liver tissue lipid peroxidation (LPO) and tissue reduced glutathione (GSH) levels. The content of strychnine and brucine was reduced upon subjecting it to the shodhana process. Similarly, it was observed that the LD 50 of unprocessed and processed seeds were 260 mg/kg and 2600 mg/ kg respectively. This indicated that the toxicity of the seeds was reduced. Treatment with CCl4 enhanced all the above-mentioned biomarkers of hepatic injury. Pre-treatment with processed (detoxified) and unprocessed seeds at 520 mg/ kg and 52 mg/ kg doses reduced the levels of biomarkers. Treatments with detoxified seeds (both traditional process and modified process) were found to be better than the unprocessed seeds. From the present study, it may be concluded that the shodhana (detoxification) process reduced the concentration of active principles and improved the therapeutic efficacy. Therefore, subjecting seeds of strychnos nux- vomica to the shodhana process before being used clinically is justifiable.
• Patel, Dinesh & Patel, Kanika & Duraiswamy, B. & Dhanabal, S.P. (2012). Phytochemical analysis and standardization of Strychnos nux-vomica extract through HPTLC techniques. Asian Pacific Journal of Tropical Disease. 2. S56– S60. 10. 1016/ S2222- 1808 (12) 60124- 8. Objective- The objective is to develop a novel qualitative and quantitative method by which we can determine different phytoconstituents of Strychnos nux-vomica L. Methods  To profile the phytoconstituents of Strychnos nux-vomica, in the present study hydroalcoholic extract of Strychnos nux-vomica was subjected to preliminary phytochemical analysis, antimicrobial activities against certain pathogenic microorganisms, solubility test, loss on drying and pH value. The extract was also subjected to quantitative analysis including total phenol, flavonoid, and heavy metal analysis. Quantitative analysis was performed through HPTLC methods using strychnine and brucine as standard markers. Results -Phytochemical analysis revealed the presence of alkaloids, carbohydrates, tannins, steroids, triterpenoids, and glycosides in the extract. The total flavonoid and phenol content of Strychnos nux-vomica L extract was found to be 0.40 % and 0.43%. The result showed that the level of heavy metals (lead, arsenic, mercury, and cadmium) compiles the standard level. Total bacterial count, yeast, and mold contents were found to be under the limit whereas E. coli and salmonella were found to be absent in the extract. The content of strychnine and brucine was found to be 4.75% and 3.91%. Conclusions- These studies provide valuable information for the correct identification and selection of the drug from various adulterations. In the future, this study will be helpful for the quantitative analysis as well as standardization of the Strychnos nux-vomica L.
• Mitra, Swarnendu & Kumar, Vijay & Bk, Ashok & Acharya, Rabinarayan & Ravishankar, Basavaiah. (2011). Comparative anti-inflammatory activity of raw and processed Kupeelu (Strychnos nux-vomica Linn.) seeds on albino rats. The ancient science of life. 31. 73- 5. Seeds of Kupeelu (Strychnos nux-vomica Linn.), a known poisonous drug, are used extensively in various Ayurvedic formulations with great therapeutic significance. Ayurveda recommends the administration of Kupeelu only after passing through specific purificatory procedures in different media like cow’s urine (Go mutra), cow’s milk (Go dugdha), cow’s ghee (Go ghrita), Kanji (thin gruel), etc. Strychnos nux vomica seeds are extensively advocated for nervous debility, paralysis, weakness of limbs, sexual weakness, dyspepsia, and dysentery, and in rheumatism where it can be assumed that besides other properties, Kupeelu may have some sort of anti-inflammatory activity too. In the present study, the powder of raw and processed Kupeelu seeds (processed/purified with Kanji i.e sour gruel) as test drugs were assessed for anti-inflammatory activity by employing Carrageenan and Formaldehyde induced hind paw edema in Wistar strain albino rats at a dose of 22.5 mg/ kg body weight orally. This study reveals that both raw and purified Kupeelu showed the presence of highly significant anti-inflammatory activity against formaldehyde-induced hind paw edema but did not have similar activity against Carrageenan-induced hind paw edema.
• Rao, Pasupuleti & Madduri, Ramanadham & Majeti, Prasad. (2008). Anti-proliferative and cytotoxic effects of Strychnos nux-vomica root extract on human multiple myeloma cell line – RPMI 8226. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 47. 283- 8. 10. 1016/ j. ft. 2008. 10. 027. Multiple myeloma (MM) is an incurable hematological malignancy with a high incidence in the elderly. The currently used chemotherapeutic drugs show severe side effects, dose-limiting toxicity, and the development of resistance. In search of novel plant-derived anti-cancer agents, Strychnos nux-vomica L. (SN) root extract was screened using the human MM-cell line, RPMI 8226. SN-extract exhibited anti-proliferative activity in a dose and time-dependent manner. The morphological assessment of SN-extract treated cells showed significant features associated with apoptosis. Cell cycle analysis using flow cytometry of cells stained with propidium iodide revealed an accumulation of cells at the sub-G (0)/ G (1) phase. In addition, disruption of mitochondrial membrane potential and subsequent leakage of mitochondrial cytochrome c was observed in SN-extract-treated myeloma cells. The anti-proliferative and cytotoxic activity could be due to the alkaloid’s strychnine and brucine, which have been identified by LC-mass spectral analysis of the SN-extract in comparison to the reference standards analyzed under identical conditions.