UNASSIGNED: Cleistanthus collinus is a poisonous shrub commonly used for deliberate self-harm in rural south India. Boiled decoction or a paste made from its leaves is used for suicide. Cleistanthoside A and Cleistanthin A are the major toxins identified from this plant. In this study, we disclose the mechanism of Cleistanthin A toxicity and concentrations of the two toxins in different extracts of Cleistanthus collinus.
UNASSIGNED: The effect of Cleistanthin A was studied on isolated goat leg arteries using two different preparations namely transverse cylinder and longitudinal strip. The influence of Cleistanthin A on peripheral vascular resistance and myocardial contractility was evaluated by rat hind limb and isolated rat heart experiments, respectively. For the quantification of toxins, five different extracts of C. collinus leaves were prepared. The extracts were subjected to analytical HPLC to quantify Cleistanthoside A and Cleistanthin A.
UNASSIGNED: Cleistanthin A increased vascular tension in transverse cylinder preparation and increased peak, trough and mean aortic pressures in the rat hind limb preparations. In isolated rat heart experiments, there was an increase in diastolic and mean ventricular pressure with a significant decrease in ventricular pulse pressure. These observations suggest that the hypotension in C. collinus poisoning patients may be due to cardiotoxicity and not due to vasodilation as is currently believed. Quantification of different extracts showed that boiled extracts had higher quantities of Cleistanthoside A whereas crushed leaf extracts yielded significantly higher amounts of Cleistanthin A.

Background The aging male population is at higher risk for benign prostatic hyperplasia (BPH) wherein increased proliferation of stromal and epithelial cells of the prostate is observed. In this study, we investigated the effect of cleistanthins A and B on the inhibition of testosterone-induced BPH in castrated rats. Methodology Male Wistar rats were divided into eight groups (n = 6) and surgical castration was performed. BPH was induced by the administration of testosterone propionate in corn oil at 5 mg/kg for four weeks. The control group received corn oil, and the model group received testosterone propionate. The standard treatment group received finasteride orally along with testosterone. Cleistanthins A and B at 0.3, 1, and 3 mg/kg were administered by oral gavage along with testosterone. After four weeks, rats were sacrificed, and prostates were weighed and assessed for histomorphological, inflammatory, apoptotic, and proliferative markers. Results Cleistanthins A and B decreased prostatic enlargement and histopathological abnormalities. Elevated serum dihydrotestosterone levels were lowered significantly in both the cleistanthin A and cleistanthin B groups compared to the BPH model group. Cleistanthins A and B significantly lowered the serum interleukin (IL)-1β and tumor necrosis factor-alpha inflammatory markers in the test groups. Western blot analysis revealed cleistanthin A downregulated the IL-6, signal transducer and activator of transcription 3/cyclin D1 signaling pathway. Both cleistanthins A and B upregulated the apoptotic markers caspase-3 and cleaved caspase-3, whereas the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen were found to be downregulated. Conclusions Both cleistanthins A and B inhibited BPH in a rat model by apoptotic induction and impeded cell proliferation.

UNASSIGNED: Cleistanthin A (CA) is an aryl naphthalene lignan, which has a potent anticancer activity by regulating the tumor microenvironment. The objective was to develop a new technique for the isolation of cleistanthin A from the acetone extract of Cleistanthus collinus utilizing reverse phase flash chromatography.
UNASSIGNED: Cleistanthus collinus leaves were shade dried, defatted using n-hexane and then macerated to obtain acetone extract which was further subjected to reverse phase flash chromatography for the isolation of cleistanthin A using the gradient mobile phase of 0.1% formic acid (v/v) in water and acetonitrile. Gradient elution of chromatographic run was performed for 80 min. The separated peaks that showed absorbance at λmax 254 nm were collected for the chemical characterization. Cell viability of the isolated cleistanthin A was studied on hepatocellular cancer cell line HePG2 and prostate cancer cell line PC3 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
UNASSIGNED: The chemical characteristics of the isolated compound cleistanthin A was further characterized using spectral techniques such as 1H and 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and electron spray ionization-tandem mass spectrometry (ESI-MS/MS). Cleistanthin A has decreased the cell viability of the HePG2 cell line to 52.25% at 32 μg/ml and PC3 cell line to 51.82% at 16 μg/ml in a dose-dependent manner.
UNASSIGNED: Cleistanthin A was successfully isolated from the natural source using reverse phase flash chromatography and the MTT assay has shown that cleistanthin A has decreased the cell viability in both the HePG2 and PC3 cell lines in a dose-dependent manner.

Plants are widely used in the traditional system of medicine and many of them can adversely affect the reproductive system. Cleistanthus collinus is a plant containing many active phytochemicals, which have the potential to be developed as a drug. The present study was aimed to evaluate the effects of an aqueous extract of C. collinus on the male reproductive system.
Male Wistar rats were treated with different doses of C. collinus (200 and 400 mg/kg, orally), or with saline for 28 days and its effect on the reproductive system was assessed. Cyclophosphamide (100 mg/kg, weekly, i.p), a well-known reproductive toxicant, was used as a positive control.
There was a significant reduction in sperm count and motility with C. collinus treatment, along with the destruction of primary spermatocytes, spermatids and reduced thickness of the basal layer. The LH, FSH and testosterone levels were reduced significantly. A reduction in the area of seminiferous tubules indicates the destruction of germ cells and Sertoli cells. C. collinus treatment increased the oxidative stress, evidenced by elevated malondialdehyde levels along with a reduction in catalase and GSH activities. The expression of BAX, BCL-2 and p53 was observed in spermatocytes, indicating an increase in apoptosis.
C. collinus can produce male reproductive toxicity, which may be mediated through alterations in hormonal levels, which in turn interferes with spermatogenesis. It may increase the expression of apoptotic factors and deplete protective antioxidant enzymes in the testis.

The present study aimed in green synthesis and characterization of silver nanoparticles (AgNPs) using the leaves of Cleistanthus collinus. The NPs showed various absorption peaks between 3402 cm-1 and 1063 cm-1. FTIR spectrum revealed the presence of OH group, alkene, aromatic hydrocarbon, aliphatic fluro compound and aliphatic chloro compounds. Scanning electron microscopic analysis revealed the particle size ranged from 30 to 50 nm. The biosynthesized NPs have potent activity against Shigella dysentriae, Staphylococcus aureus and Bacillus subtilis and the zone of inhibition was 21 ± 1, 20 ± 2, 16 ± 2 mm, respectively. Toxicity of the synthesized NPs was tested on green gram (Vigna radiata) seed at various concentrations (20-100%) and germination was induced by NPs treated seeds. Shoot length and root length was higher in NPs treated plant than control plant (p < 0.01). Elevated level of catalase (CAT) and superoxide dismutase (SOD) and about 13% CAT and 7% SOD activity registered than control. Superoxide dismutase activity of root and shoot varied based on the dosage of AgNPs (p < 0.01). Also, the NPs (1%) showed significant larvicidal activity on Aedes aegypti and 100% mortality was achieved after 24 h treatment. The green synthesized NPs reduced methylene blue and 4-nitrophenol significantly (p < 0.01). The colouration of methylene blue and 4-nitrophenol were considerably reduced after 60 min showed the potential of dye degrading ability.

How to cite this article: Mohan A, Harikrishna J. Cleistanthus collinus Poisoning. Indian J Crit Care Med 2019;23(Suppl 4):S256-S259.

OBJECTIVE: To investigate the toxicological effects of cleistanthin A and cleistanthin B using sub-chronic toxicity testing in rodents.
METHODS: Cleistanthins A and B were isolated from the leaves of Cleistanthus collinus. Both the compounds were administered orally for 90 days at the concentration of 12.5, 25 and 50 mg/kg, and the effects on blood pressure, biochemical parameters and histology were assessed. The dose for sub-chronic toxicology was determined by fixed dose method according to OECD guidelines.
RESULTS: Sub-chronic toxicity study of cleistanthins A and B spanning over 90 days at the dose levels of 12.5, 25 and 50 mg/kg (once daily, per oral) revealed a significant dose dependant toxic effect in lungs. The compounds did not have any effect on the growth of the rats. The food and water intake of the animals were also not affected by both cleistanthins A and B. Both the compounds did not have any significant effect on liver and renal markers. The histopathological analysis of both cleistanthins A and B showed dose dependent morphological changes in the brain, heart, lung, liver and kidney. When compared to cleistanthin A, cleistanthin B had more toxic effect in Wistar rats. Both the compounds have produced a dose dependent increase of corpora amylacea in brain and induced acute tubular necrosis in kidneys. In addition, cleistanthin B caused spotty necrosis of liver in higher doses.
CONCLUSIONS: The present study concludes that both cleistanthin A and cleistanthin B exert severe toxic effects on lungs, brain, liver, heart and kidneys. They do not cause any significant pathological change in the reproductive system; neither do they induce neurodegenerative changes in brain. When compared to cleistanthin A, cleistanthin B is more toxic in rats.

Cleistanthus collinus, also known as Oduvanthalai in Tamil, is the most commonly encountered plant poison in southern India. The leaves are used for poisoning humans (suicide or homicide) and animals (cattle and fish) and as an abortifacient, especially in rural south India. Although this poisoning is commonly reported in adults, data regarding the use of N-acetylcysteine in pediatric poisoning is lacking. We report two previously healthy male siblings of pediatric age group who ingested the liquid extracted from crushed leaves of this plant given to them by their mother as a means of deliberate harm. Both patients developed distal renal tubular acidosis, with hypokalemia. The younger sibling also developed myocardial toxicity. Other significant findings noted include hypocalcemia, hypomagnesemia and elevated liver enzymes. Both patients received supportive care along with N-acetylcysteine infusion, and showed complete recovery within 10 days.

Cleistanthus collinus is an extremely toxic plant poison. We report a case of suicidal ingestion of boiled water decoction of C. collinus where the patient presented with abdominal pain and giddiness. There was persistent metabolic acidosis and fluctuation in the level of serum potassium. The ECG changes indicated a probable myocardial injury with conduction abnormality. At autopsy, the viscera were found to be congested. The toxins were detected in the viscera and blood by TLC and HPLC. Cleistanthin A and B, collinusin, and diphyllin are the principal toxic constituents of the plant. Consumption of a boiled decoction of leaves is highly toxic and, medical management of patients is mainly supportive because the molecular mechanisms of toxin action are unknown. In the recent years, C. collinus has created a considerable amount of interest because of its complex metabolites and their cytotoxic activities. Through this study, the authors have tried to highlight different properties pertaining to C. collinus.

There is paucity of information on human studies about Cleistanthus collinus (Oduvanthalai) poisoning at global level. The present study was done to find out the pattern and outcomes with acute poisoning of this plant poison. Retrospective record based study was conducted among acute C. collinus (Oduvanthalai) poisoning cases admitted between January 2010 and December 2010 in a tertiary care teaching hospital in South India. A total of 51 cases were analyzed with 52.9% of them being females and 51% belonged to 21-40 years age group. Interpersonal conflict was the stressor for poisoning in 76% cases. Mortality rate was 17.6% with a median duration of 3.5 days from time of ingestion. Majority of the patients who died during hospitalization had ingested decoction (77.8%), and had neurological manifestations (77.8%), hypokalemia (77.8%), neutrophilia (66.7%), leucocyotosis (55.6%) and elevated blood urea (77.8%). It was found that lower potassium level, white blood cell and neutrophil count were significantly associated with mortality due to poisoning.