Withametelin: a biologically active withanolide in cancer, inflammation, pain and depression

Baig, Muhammad Waleed; Nasir, Bakht; Waseem, Durdana; Majid, Muhammad; Khan, Muhammad Zafar; Haq, Ihsan‐ul

doi:10.1016/j.jsps.2020.09.021

Cited by 27 publications

(12 citation statements)

References 60 publications

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“…FRSA of the extracts was evaluated using methanol solution of DPPH ( Ahmedet al, 2017 , Baiget al, 2020 ). An aliquot of 10 µl of the extracts (4 mg/ml DMSO) were added to respective wells of 96 well plate.…”

Section: Methodsmentioning

confidence: 99%

Phytochemical analysis and comprehensive evaluation of pharmacological potential of Artemisia brevifolia Wall. ex DC

Kazmi

Zahra

Nasar

et al. 2022

Saudi Pharmaceutical Journal

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Section: Methodsmentioning

confidence: 99%

Phytochemical analysis and comprehensive evaluation of pharmacological potential of Artemisia brevifolia Wall. ex DC

Kazmi

Zahra

Nasar

et al. 2022

Saudi Pharmaceutical Journal

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“…Withanolides are steroidal lactones that possess significant immunomodulatory, antimicrobial, antioxidant, and anti-inflammatory properties [ 29 ]. Withametelin (WMT) is a potent withanolide derivative obtained from the leaves of Datura innoxa that exhibit diverse pharmacological properties, including anti-inflammatory, antioxidant, antidepressant, and anticancer [ 30 , 31 , 32 ]. The leaves of Datura innoxa have been used in traditional medicine to treat seizures and nerve pain (facial pain and headache) [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

Khan

Shal

Khan

et al. 2021

IJMS

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Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 μg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1–10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.

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“…Ligands and heteroatoms were removed and proteins were optimized and minimized using UCSF Chimera software to obtain structurally correct protein. Docking was performed using the Pyrx-virtual screening tool, binding affinities were saved as CSV files and Discovery studio was used to visualize the final protein–ligand interactions [ 48 ].…”

Section: Methodsmentioning

confidence: 99%

Profiling of Antifungal Activities and In Silico Studies of Natural Polyphenols from Some Plants

et al. 2021

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A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica. The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani. Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (Kd, −9.4 and −8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections.

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Withametelin: a biologically active withanolide in cancer, inflammation, pain and depression

Cited by 27 publications

References 60 publications

Phytochemical analysis and comprehensive evaluation of pharmacological potential of Artemisia brevifolia Wall. ex DC

Phytochemical analysis and comprehensive evaluation of pharmacological potential of Artemisia brevifolia Wall. ex DC

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

Profiling of Antifungal Activities and In Silico Studies of Natural Polyphenols from Some Plants

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