Asian Pacific Journal of Tropical Biomedicine

Number 13(9), 2023

369-377
Plant-derived natural compounds in the treatment of arsenic-induced toxicity

Authors: Bhattacharya, Sanjib

Abstract

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Arsenic toxicity, imposed mainly by arsenic-contaminated groundwater, is considered a critical threat to global communal health, as there is no specific and proven conventional therapy for chronic arsenic toxicity, i.e., arsenicosis, which is an insidious global public health menace affecting 50 countries. Alternative options should, therefore, be explored for the mitigation of arsenicosis. Literature survey reveals several natural compounds from plants possess significant protective efficacy against arsenic toxicity in chiefly preclinical and few clinical investigations. The studies on the ameliorative effects of plant-derived natural compounds against arsenic toxicity published in the last 25 years are collated. Forty-eight plant-based natural compounds possess alleviative effects on experimental arsenic-induced toxicity in animals, six of which have been reported to be clinically effective in humans. A potential nutraceutical or therapeutic candidate against arsenicosis for humans may thus be developed with the help of recent advancements in research in this area, along with the currently available treatments.

378-383
Metabolomics in drug discovery: Restoring antibiotic pipeline

Authors: Azhar, Faiza; Busharat, Mariam; Chaudhary, Shah Rukh Arshad; Waheed, Zainab; Jamil, Muhammad Nauman

Abstract

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Metabolomics has emerged as a valuable tool in drug discovery and development, providing new insights into the mechanisms of action and toxicity of potential therapeutic agents. Metabolomics focuses on the comprehensive analysis of primary as well as secondary metabolites, within biological systems. Metabolomics provides a comprehensive understanding of the metabolic changes that occur within microbial pathogens when exposed to therapeutic agents, thus allowing for the identification of unique metabolic targets that can be exploited for therapeutic intervention. This approach can also uncover key metabolic pathways essential for survival, which can serve as potential targets for novel antibiotics. By analyzing the metabolites produced by diverse microbial communities, metabolomics can guide the discovery of previously unexplored sources of antibiotics. This review explores some examples that enable medicinal chemists to optimize drug structure, enhancing efficacy and minimizing toxicity via metabolomic approaches.

384-392
Beta-glucan protects against isoproterenol-induced cardiac remodeling by regulating the ACE-AT1R axis and attenuates cardiac inflammation and apoptosis

Authors: Roy, Anitha; Neelakantappa, Vasantha Mallenahalli; Ganesan, Jayashree; Ramajayam Asokan, Balakrishnan; Kulandaivel, Srinivasan; Uddandrao, V. V. Sathibabu; Singaravel, Sengottuvelu

Abstract

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Objective: To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats, and elucidate the underlying mechanism. Methods: Rats were orally pretreated with beta-glucan (40 mg/kg body weight) for 30 d, and isoproterenol (20 mg/100 g body weight) was administered on days 31 and 32. The effects of beta-glucan on markers of cardiac injury, hemodynamic changes, production of proinflammatory cytokines, and the corresponding mRNA expressions were evaluated. In addition, histological analysis was performed. Results: Pretreatment with beta-glucan prevented isoproterenol-induced cardiac injury by preserving the structural and functional integrity of the plasma membrane and attenuating the production of proinflammatory cytokines (NF-κB, TNF-α, IL-6, IL-Ιβ, and IFN-γ) in the heart. Moreover, beta-glucan significantly downregulated the mRNA expression of ACE, AT1R, TNF-α, IL-6, NF-κB, caspase-3, TLR-4, and Bax, and upregulated Bcl-2 in the heart. At the same time, pretreatment with beta-glucan alleviated myocardial damage as reflected in a reduction in myonecrosis, edema, and erythrocyte extravasation with almost imperceptible inflammation. Conclusions: Beta-glucan can protect against isoproterenol-induced cardiotoxicity by attenuating cardiac inflammation and apoptosis and regulating the ACE-AT1R axis, thereby preventing cardiac remodeling.

393-402
Decreased TRPM7 alleviates high glucose-induced renal tubular epithelial cell injury by inhibiting the HMGB1/TLR4 signaling pathway

Authors: Feng, Wei; Cao, Zheng-Yong; Guan, Fu-Min; Chen, Hong

Abstract

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Objective: To explore the regulatory mechanism of transient receptor potential melastatin-7 (TRPM7) in high glucose-induced renal tubular epithelial cell injury. Methods: The expression of TRPM7 in the serum of diabetic nephropathy patients and high glucose-induced HK-2 cells was detected by RT-qPCR. Then, the TRPM7 interference vector was constructed, and the downstream high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway proteins were detected. Next, in addition to interference with TRPM7 expression, overexpression of HMGB1 in high glucose-induced HK-2 cells was performed. Cell activity, apoptosis, oxidative stress levels, and inflammation levels were determined by CCK8, TUNEL, Western blotting, immunofluorescence and related kits. Results: TRPM7 expression was upregulated in the serum of diabetic nephropathy patients and high glucose-induced HK-2 cells. Interference with TRPM7 reduced cell damage, epithelial-mesenchymal transition, oxidative stress, and inflammatory response in high glucose-induced HK-2 cells via inhibiting the HMGB1/TLR4 signaling pathway. However, the effects induced by TRPM7 silencing were abrogated by HMGB1 overexpression. Conclusions: Decreased TRPM7 alleviates high glucose-induced renal tubular epithelial cell injury by inhibiting the HMGB1/TLR4 signaling pathway. Further animal experiments and clinical trials are warranted to verify its effect.

403-410
Inhibitory effect of Cyrtomium falcatum on melanogenesis in α-MSH-stimulated B16F10 murine melanoma cells

Authors: Zhou, Xian-Rong; Oh, Jung Hwan; Karadeniz, Fatih; Lee, Hyunjung; Kim, Hyo Eun; Jo, Migeon; Seo, Youngwan; Kong, Chang-Suk

Abstract

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Objective: To explore the anti-melanogenic potential of Cyrtomium falcatum. Methods: The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity, melanin content, and the expressions of melanogenesis-related genes and proteins were analyzed in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. Results: α-MSH treatment significantly increased tyrosinase activity, and extracellular and intracellular melanin content, as well as the expression levels of tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)-1, and TRP-2 in B16F10 cells. Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase, MITF, TRP-1, and TRP-2 in a dose-dependent manner. Conclusions: Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.