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Background: Paclitaxel (PTX) is a known chemotherapeutic agent, used to treat different types of cancers. However, it leads to neuropathic pain in a sizeable proportion of the patients. Currently, analgesics, opioids, tricyclic antidepressants and anticonvulsants are prescribed for PTX-mediated chemotherapy-induced peripheral neuropathy (CIPN). However, these treatments have acute side-effects, creating a need for safer alternative treatment option. Method: PTX-mediated CIPN has nociceptive outcomes, like, allodynia and hyperalgesia with an underlying inflammatory and oxidative causes. The herbo-mineral medicine, Divya-Peedantak-Vati (DPV) is known for its effectivity against joint pain and inflammatory disorders in Ayurveda, a traditional Indian system of medicine. Therefore, anti-neuropathic potential of DPV was assessed in PTX-induced neuropathic CD-1 mice, with allodynia and hyperalgesia, as the clinically relevant endpoints. DPV was investigated for its nociception-modulatory and anti-inflammatory effects under in vivo and in vitro conditions. Results: DPV treatment exhibited notable anti-allodynic and anti-hyperalgesic effects in a dose dependent manner, and displayed prominent anti-oxidant effects in the sciatic nerve of the study animals. It also moderated, in a dose dependent manner, the levels of cytokine, interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNF-α) induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. Conclusions: The novelty of this study lies in the demonstration of the anti-neuropathic potential and elucidation of anti-neuropathic mode-of-action of an herbal medicine. Taken together, this study showed that DPV could well be an effective alternative healing option for PTX-mediated CIPN.

The widely used cancer treatment, chemotherapy, causes severe long-term neuropathic pain in 30–40% cases, the condition clinically known as chemotherapy-induced peripheral neuropathy (CIPN). Approved conventional analgesics are sometimes ineffective, while others like opioids have undesirable side effects like addiction, seizures, and respiratory malfunctioning. Tricyclic antidepressants and anticonvulsants, although exhibit anti-allodynic effects in neuropathy, also have unpleasant side effects. Thus, alternative medicines are being explored for CIPN treatment. Despite scattered reports on different extracts from different plants having potential anti-allodynic effects against CIPN, no established medicine or formulation of herbal origin exists. In this study, efficacy of an herbal decoction, formulated based on ancient medicinal principles and protocols for treating neuropathic pain, Divya-Peedantak-Kwath (DPK), has been evaluated in a paclitaxel (PTX)-induced peripheral neuropathic mouse model. We observed that DPK has prominent anti-allodynic and anti-hyperalgesic effects and acts as a nociceptive modulator for CIPN. With exhibited antioxidative effects, DPK restored the redox potential of the sciatic nerves to the normal. On histopathological evaluation, DPK prevented the PTX-induced lesions in the sciatic nerve, in a dose-dependent manner. It also prevented inflammation by modulating the levels of pro-inflammatory cytokines involved in CIPN pathogenesis. Our observations evinced that DPK can alleviate CIPN by attenuating oxidative stress and concomitant neuroinflammation through immune modulation.

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.

Purpose: 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., Competing Interests: The test articles were 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; he reports no other potential conflicts of interest for this work. Besides, providing the test article, Divya Pharmacy was not involved in any aspect of this study. All other authors report no conflicts of interest for this work., (© 2022 Balkrishna et al.)

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.)

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 IC(50) value. Results showed that the aqueous and methanol extracts exhibited significant DPPH radicals scavenging activity with an IC(50) value 342.59 ± 19.59, 283.24 ± 12.28 µg/mL respectively. Nitric oxide radicals were significantly scavenged by the aqueous and methanol extracts (IC(50) = 250.12 ± 10.66; 328.29 ± 3.74 µg/mL). Lipid peroxidation induced by the Fe(2+) was inhibited by the aqueous extract with low IC(50) value (97.29 ± 2.05 µg/mL) as compared to methanol extract (IC(50) = 283.74 ± 5.70 µg/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.