Assessment of the systemic toxicity of Laghu vishagarbha taila, an Ayurvedic medicated oil formulation after dermal exposure.

Laghu vishagarbha taila (LVT) is a medicated oil preparation used in the Ayurvedic system of medicine and applied topically for the treatment of painful musculoskeletal and inflammatory disorders. It contains some mildly poisonous phytoconstituents which may show untoward effects upon application. The present study evaluated the toxicity of LVT in the acute, subacute, and subchronic dermal toxicity study in Wistar rats. LVT was tested for its compliance using physicochemical and analytical parameters as per standard methods prescribed in Ayurvedic Pharmacopoeia of India, while acute, subacute, and subchronic toxicity studies were carried out as per OECD 402, 410, and 411 guidelines, respectively. In the acute dermal toxicity study, a single dose of LVT (2000 mg/kg) was applied topically to rats, while in subacute and subchronic dermal toxicity study, the rats were topically applied LVT (1000 mg/kg) up to 28 and 90 days, respectively. LVT did not cause any alterations in clinical signs and no mortality or moribund stage was observed. The change in weekly body weight was insignificant compared with the vehicle control group. In subacute and subchronic dermal toxicity study, there were no significant changes in behavior, body weight, feed consumption, biochemical and hematological parameters, organ weight, and histological parameters compared with vehicle control rats. Topical application of single and repeated doses of LVT in rats did not exhibit adverse effects and suggests that the LD50 of LVT is more than 2000 mg/kg in the acute dose and NOAEL is more than 1000 mg/kg/day in repeated dose application.

Oral toxicity evaluation of gokshuradi guggulu, an ayurvedic formulation.

Gokshuradi guggulu is an important classical polyherbal formulation used in Ayurvedic system of medicine for the treatment of various chronic diseases like kidney stones and diabetes. However, no scientific attempts were made to evaluate its oral toxicity. Hence, the present study evaluated the acute and 28 days repeated dose sub-acute oral toxicities of gokshuradi guggulu in rats. Gokshuradi guggulu was tested for its compliance using physicochemical and analytical parameters as per standards prescribed in Ayurvedic Pharmacopeia of India. In acute oral toxicity study, Wistar rats were orally administered a single dose of gokshuradi guggulu (2700 mg/kg) and clinical signs and mortality or moribund stage were observed for 14 days along with weekly body weight. On day 15, the rats were euthanized and the gross morphology was carried out during necropsy. In sub-acute (repeated dose) oral toxicity study, the rats were orally administered gokshuradi guggulu (270, 1350 and 2700 mg/kg) once daily up to 28 days. Clinical signs and mortality or moribund stage, weekly body weight, weekly feed and water consumptions, biochemical and hematological investigations, urine analysis, and major organ weights and histopathology were carried out. In acute and sub-acute toxicity studies, gokshuradi guggulu administration did not show any alteration in parameters or any adverse effect as compared to vehicle treated group. There was no mortality or moribund state observed in any group in both studies. Administration of gokshuradi guggulu in acute and 28 days repeated doses did not exhibit any toxicity or adverse effect at the doses used and NOAEL was found to be 2700 mg/kg.

Nephroprotective potential of Anogeissus latifolia Roxb. (Dhava) against gentamicin-induced nephrotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark of Anogeissus latifolia Roxb. (Family: Combretaceae) is used traditionally and ethnomedicinally for correction of kidney disorders. AIM OF THE STUDY: The present study demonstrates the nephroprotective potential of stem bark of A. latifolia Roxb. MATERIALS AND METHODS: The HPTLC fingerprint and HPLC analysis were carried out to standardize the ethanolic extract of stem bark of A. latifolia (ALEE) using ellagic acid as a marker. Nephrotoxicity was induced in adult Wistar albino rats by gentamicin (100 mg/kg, intraperitoneally for 8 days) and they were treated with ALEE (100, 200 and 400 mg/kg, orally for 8 days), ellagic acid (10 mg/kg, orally for 8 days) and cystone syrup (5 ml/kg, orally), a standard reference a polyherbal formulation. Urine volume, serum and urine levels of creatinine, urea and uric acid, oxidative stress parameters (lipid peroxidation, catalase, superoxide dismutase and reduced glutathione), inflammatory markers (TNF-α and IL-6) and kidney weight along with its histological changes were studied in experimental animals. RESULTS: HPTLC, HPLC and LC-MS analysis of ALEE revealed the presence of ellagic acid and other various phytoconstituents. Administration of gentamicin caused significant increase in urine output and kidney weight, elevated biochemical, inflammatory and oxidative stress parameters as well as caused histological damage in the kidney tissue. These parameters were attenuated by the concurrent treatment with ALEE and ellagic acid. The effects were comparable to cystone. CONCLUSION: Present investigations concluded that ALEE exhibited nephroprotective potential and validated the traditional use of stem bark of A. latifolia in kidney disorders. The nephroprotective effect may be attributed to the antioxidant and anti-inflammatory phytoconstituents in ALEE.

Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19.

The present study aimed to investigate the binding affinity of andrographolide and its derivative i.e., 14-deoxy-11,12-didehydroandrographolide with targets related to COVID-19 and their probable role in regulating multiple pathways in COVID-19 infection. SMILES of both compounds were retrieved from the PubChem database and predicted for probably regulated proteins. The predicted proteins were queried in STRING to evaluate the protein-protein interaction, and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profile of each compound was evaluated using MolSoft and admetSAR 2.0, respectively. Molecular docking was carried using Autodock 4.0. Andrographolide and its derivative were predicted to have a high binding affinity with papain-like protease, coronavirus main proteinase, and spike protein. Molecular dynamics simulation studies were performed for each complex which suggested the strong binding affinities of both compounds with targets. Network pharmacology analysis revealed that both compounds modulated the immune system by regulating chemokine signaling, Rap1 signaling, cytokine-cytokine receptor interaction, MAPK signaling, NF-kappa B signaling, RAS signaling, p53 signaling, HIF-1 signaling, and natural killer cell-mediated cytotoxicity. The study suggests strong interaction of andrographolide and 14-deoxy-11,12-didehydroandrographolide against COVID-19 associated target proteins and exhibited different immunoregulatory pathways.

Beneficial effect of standardized extracts of Amorphophallus paeoniifolius tuber and its active constituents on experimental constipation in rats.

The tubers of Amorphophallus paeoniifolius (Elephant foot yam), principally consumed as crop food and vegetables, are used in ethno-medicinal practices in mitigation of constipation and piles. Hence, present study evaluated the effect of tubers of A. paeoniifolius and its active constituents glucomannan and betulinic acid on experimentally-induced constipation. The tuber and its extracts were standardized as per Ayurvedic Pharmacopoeia of India and physicochemical constants were found within the pharmacopoeial limit. HPTLC fingerprint profile of extracts has been developed using suitable mobile phase. Methanolic extract was subjected to column chromatography. The isolated phytoconstituents were characterized by FT-IR, NMR and MS and identified as betulinic acid and ß-sitosterol. Functional constipation was induced in rats by oral administration of loperamide (3 mg/kg) for first 3 consecutive days. The rats were orally treated with methanolic and aqueous tuber extracts in the doses of 125, 250 and 500 mg/kg, glucomannan (300 mg/kg) and betulinic acid (1.5 mg/kg) for 7 days. The parameters viz. number of stools, wet weight of stools and moisture content of stools and intestinal transit were studied. Treatment with tuber extracts, glucomannan and betulinic acid showed significant (p < 0.05) increase in fecal parameters and intestinal transit in constipated rats. The effects were comparable to standard laxative drug, sodium picosulfate (5 mg/kg, orally). The results indicated that tuber extracts and its active constituents showed laxative effect and relieved constipation. It is concluded that tuber of A. paeoniifolius exhibited beneficial effect in functional constipation possibly through its laxative action. The study validates its ethno-medicinal use in correction of constipation. The principal constituents, betulinic acid and glucomannan in tuber extracts might have played important role in relieving the constipation.

Evaluation for substitution of stem bark with small branches of Myrica esculenta for medicinal use - A comparative phytochemical study.

BACKGROUND: Over exploitation of many traditional medicinal plants like Myrica esculenta has become a threat and in the near future, many medicinal plants may be unavailable for use of industry. OBJECTIVE: Present study outlines the concept of plant part substitution. Stem bark and small branches of M. esculenta are compared on the basis of physicochemical analysis, phytochemical analysis, total phenolic contents, total flavonoid contents and high performance thin layer chromatography (HPTLC) to evaluate the possibilities of using small branches in place of stem bark. MATERIAL AND METHODS: Physicochemical parameters and preliminary phytochemical screening were carried out using standard methods. Total phenolic and total flavonoid contents were estimated spectrophotometrically using Folin-Ciocalteu and aluminum chloride method, respectively. CAMAG HPTLC system equipped with semi-automatic applicator was used for HPTLC profiling. n-Hexane, ethyl acetate and ethanol extracts of stem bark and small branches were developed in suitable mobile phase using standard procedures and visualized in UV 254 and 366 nm and in white light after derivatization within anisaldehyde-sulphuric acid reagent. RESULTS: Phytochemical analysis and HPTLC profile of different extracts showed the presence of almost similar phytochemicals in both stem bark and small branches. CONCLUSION: Similarities in phytochemical analysis and HPTLC profile of various extracts suggests that small branches may be used in place of stem bark. The study provides the base for further study to use small branches as a substitute of stem bark of M. esculenta.

Management of difficult airway in penetrating cervical spine injury.

Management of airway in trauma victim with penetrating cervical/thoracic spine injury has always been a challenge to the anaesthesiologist. Stabilisation of spine during airway manipulation, to prevent any further neural damage, is of obvious concern to the anaesthesiologist. Most anaesthesiologists are not exposed to direct laryngoscopy and intubation in lateral position during their training period. Tracheal intubation in the lateral position may be unavoidable in some circumstances. Difficult airway in an uncooperative patient compounds the problem to secure airway in lateral position. We present a 46-year-old alcoholic, hypertensive, morbidly obese person who suffered a sharp instrument (screwdriver) spinal injury with anticipated difficult intubation; the case was managed successfully.

Spectrophotometric determination of Rauwolfia alkaloids: estimation of reserpine in pharmaceuticals.

A simple, sensitive and economically viable spectrophotometric method for the determination of some Rauwolfia alkaloids (ajmaline, ajmalicine, reserpine and yohimbine-HCl) has been developed. The method involves the oxidation of Rauwolfia alkaloids by iron(III) and subsequent complexation of iron(II) with 1,10-phenanthroline, forming a red-colored complex having the maximum absorbance at 510 nm. The method is applied to the determination of reserpine in tablets of pharmaceutical formulations. The common excipients do not interfere with the proposed method. A statistical comparison of these results with those of a reported method shows good agreement and indicates no significant difference in the precision.