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Acharya Balkrishna,1,2 Sudeep Verma,1 Sachin Sakat,1 Kheemraj Joshi,1 Siva K Solleti,1 Kunal Bhattacharya,1 Anurag Varshney1,2 1Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, 249 405, Uttarakhand, India; 2Department of Allied and Applied Sciences, University of Patanjali, Patanjali YogPeeth, Haridwar, 249 405, Uttarakhand, IndiaCorrespondence: Anurag Varshney, Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar, 249405, Uttarakhand, India, Tel +91 1334-244107 x7458, Fax +91 1334 244805, Email anurag@prft.co.inPurpose: Atopic dermatitis (AD) is a chronic inflammatory disease that varies in signs and symptoms in different individuals. General symptoms include dryness of the skin, itching, and development of red to brownish-gray patches. Divya-Kayakalp-Vati (DKV) and -Oil (DKO) are Indian polyherbal compositions prescribed for treating inflammatory skin diseases. In the present study, we evaluated the anti-inflammatory efficacy of DKV and DKO co-treatment (DKV-O) in ameliorating Oxazolone (OXA)-stimulated AD-like inflammation and pro-inflammatory cytokine release in a Swiss albino mouse model.Methods: Phytochemical profiling of the DKV and DKO were done using Liquid Chromatography-Mass Spectroscopy (LC-MS) QToF. Swiss albino mice were sensitized for 7 days and treated with OXA in their ear region. Stimulated and control animals were orally treated with DKV and topically with DKO. Anti-inflammatory efficacy of DKV-O was determined in OXA-treated animals through physiological, histopathological, and biochemical parameter analysis.Results: DKV and DKO formulations individually contained 39 and 59 phytochemicals, respectively. Many of the phytochemicals have been reported to have anti-inflammatory activities. In the OXA-sensitized Swiss albino mice, combined treatment with DKV-O, and separately with Dexamethasone (positive control) significantly reduced the OXA-stimulated ear edema, biopsy weight, and epidermal thickness. DKV-O further reduced OXA-stimulated induction of inflammatory lesions, neutrophil influx, and release of Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and myeloperoxidase.Conclusion: Finally, DKV-O co-treatment showed good pharmacological effects in ameliorating AD-like inflammation through the modulation of inflammatory cell influx and release of soluble mediators. Therefore, DKV-O treatment can be used as a suitable polyherbal therapeutic against AD-like inflammatory diseases.Keywords: inflammation, oxazolone, phytochemical profile, pro-inflammatory cytokines, histopathological analysis, biochemical analysis

The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the antioxidant activity of aqueous and methanol extracts of Erythrina indica Lam leaves by in vitro methods viz. 1, 1-Diphenyl-2-Picrylhydrazyl, nitric oxide radical scavenging activity, and inhibition of lipid peroxidation by thiobarbituric acid reactive substances (TBARS) method on isolated rat liver tissues. Quantitative analysis of antioxidative components like total amount of phenolics, flavonoids, and flavonols were estimated using the spectrophotometric method. Linear regression analysis was used to calculate the IC50 value. Results showed that the aqueous and methanol extracts exhibited significant DPPH radicals scavenging activity with an IC50 value 342.59 ± 19.59, 283.24 ± 12.28 mg/mL respectively. Nitric oxide radicals were significantly scavenged by the aqueous and methanol extracts (IC50 5 250.12 ± 10.66; 328.29 ± 3.74 mg/mL). Lipid peroxidation induced by the Fe21 was inhibited by the aqueous extract with low IC50 value (97.29 ± 2.05 mg/mL) as compared to methanol extract (IC50 5 283.74 6 5.70 mg/mL). Both the extracts were exhibited similar quantities of total phenolics. Total flavonoids were found to be in higher quantities than total flavonols in aqueous extract as compared to methanol extract. From the results, it is concluded that the aqueous and methanol extracts of E. indica leaves possesses significant antioxidant activity that may be due to the presence of flavonoids and related polyphenolic compounds. [ABSTRACT FROM AUTHOR]

In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1 mg per plate), with or without metabolic activation, were negative. The micronucleus test with TK6 (human lymphoblastoid) cells, at doses up to 500 µg/mL, with or without metabolic activation, also gave negative results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Canagliflozin, Dapagliflozin, and Empagliflozin, glucagon-like peptide-1 receptor agonists, are indicated for managing type II diabetes. Although the genotoxicity profiles of these drugs are well-explored, limited information exists regarding the genotoxic potential of their impurities. In this investigation, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin underwent both in silico and in vitro assessments for mutagenic potential. Tester strains of Salmonella typhimurium and Escherichia coli were subjected to the Ames test, utilizing concentrations of up to 1 µg per plate, with and without the presence of metabolic activation. Evaluation of micronucleus induction in TK6 cells was conducted through a micronucleus test, exploring concentrations up to 500 µg/mL, with or without the presence of exogenous metabolic activation. Under the specific test conditions, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin showed no evidence of mutagenicity or clastrogenicity, establishing their in vitro classification as nonmutagenic. These findings align with negative in silico predictions from quantitative structure-activity relationship (QSAR) analyses for mutagenicity and genotoxicity of the dimer impurities. Collectively, these studies contribute clinically relevant safety information by confirming that the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin are nonmutagenic and nongenotoxic, emphasizing the consistency between in silico and in vitro data.

Background: We detected yellow-green fluorescence in the face, hair and lunulae of patients using favipiravir., Aim: We evaluated the frequency and intensity of favipiravir-associated fluorescence., Patients/methods: The participants comprised patients who had taken at least a single dose of favipiravir and been examined no later than 30 days after the last dose. The gender, age, body mass index (BMI), Fitzpatrick's skin-type, hair color, N-acetylcysteine use, presence and the intensity of fluorescent reflection under Wood's light in the lunulae of the fingernails, hair, and the face were recorded., Results: There were 275 patients, 144 (52.4%) of whom were women. 165 (57.9%) had used treatment for a maximum of 5 days, 99 (34.7%) for 6-10 days, and 21 (7.4%) for more than ten days. Using more than 22 tablets of favipiravir increased the probability of detecting fluorescence in the lunulae by 6.72 (2.61-17.23) times. Using more than 28 tablets increased the risk of fluorescence in hair and the T-zone by 5.92 (2.43-14.71) and 2.88 (1.11-7.47) times, respectively. No relationship was found between the fluorescence intensity in any localization and the total dose. However, we determined a negative correlation between the elapsed time after the last dose and the fluorescence intensity in the lunulae and the T-zone (p=0.036; p=0.031; respectively). It was noted that BMI negatively correlated with the fluorescence intensity in the lunulae (p=0.001). Skin type was related to intensity for all localizations (p<0.001). Fluorescence was found in the lunulae with significantly less frequency in patients using N-acetylcysteine (p=0.040)., Conclusions: We must be aware of favipiravir-induced phototoxicity., (© 2021 Wiley Periodicals LLC.)

Background and Aim: Psoriasis (Ps) is a chronic skin inflammatory disorder, that progresses to scaly-red dermal plaque formations associated with inflammation. Divya-Kayakalp-Vati (DKV) and Divya-Kayakalp-Oil (DKO) are traditional Ayurveda herbo-mineral formulations, that are prescribed for the treatment of inflammatory dermal ailments. In the present study, we evaluated the efficacy of Divya-Kayakalp-Vati and Divya-Kayakalp-Oil (DKV-O) combined treatment in ameliorating Ps-like skin inflammation under in-vitro and in-vivo conditions., Experimental Procedure: Efficacy of DKV-O was analyzed in λ-carrageenan-treated Wistar rats paw edema and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated CD-1 mouse ear edema models through physiological and histopathological analysis. Mode of action for the DKV-O was studied in LPS-stimulated THP-1 cells through pro-inflammatory cytokine analysis. Observed effects were correlated to the phytochemicals constituents of DKV-O analyzed using the HPLC method., Result and Conclusion: DKV and DKO formulations were individually found to contain phytochemicals Gallic acid, Catechin, Berberine, Curcumin, Phenol and Benzoic acid. DKV-O treatment significantly reduced the paw volume and edema in Wistar rats stimulated through λ-carrageenan-treatment. Furthermore, DKV-O treatment significantly reduced the ear edema and enhanced biopsy weight, epidermal thickness, inflammatory lesions and influx of neutrophils stimulated by TPA-treatment in CD-1 mice. DKV alone ameliorated the LPS-stimulated release of Interleukin (IL)-6, IL-17A, IL-23, and Tumor Necrosis Factor-alpha cytokines in the THP-1 cells.Taken together, DKV-O showed good efficacy in ameliorating acute systemic inflammation stimulated by effectors such as, λ-carrageenan and TPA in animal models. Hence, Divya-Kayakalp-Vati and Divya-Kayakalp-Oil co-treatment can be further explored as an anti-inflammatory treatment against dermal diseases like psoriasis and atopic dermatitis., Competing Interests: The test article was sourced from Divya Pharmacy, Haridwar, Uttarakhand, India. Acharya Balkrishna is an honorary trustee in Divya Yog Mandir Trust, Haridwar, India. In addition, he holds an honorary managerial position in Patanjali Ayurved Ltd., Haridwar, India. Besides, providing the test article, Divya Pharmacy was not involved in any aspect of this study. All other authors have no conflict of interest to declare., (© 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)