Asian Pacific Journal of Tropical Biomedicine

378-383

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

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.

393-402

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

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.

339-347

Authors: Jayasingha, Jayasingha Arachchige Chathuranga Chanaka; Lee, Kyoung Tae; Choi, Yung Hyun; Kim, Gi-Young

Objective: To evaluate the effects of an aqueous extract of Protaetia brevitarsis (AEPB) on the growth of zebrafish and preosteoblast MC3T3-E1 cells. Methods: The effects of AEPB on the linear growth and the expression of growth-related genes in zebrafish and MC3T3-E1 cells were assessed using various molecular techniques. Furthermore, the involvement of the mammalian target of rapamycin (mTOR) pathway in AEPB-induced growth was investigated by employing the mTOR inhibitor rapamycin. Results: AEPB administration led to a significant and dose-dependent increase in zebrafish larvae growth over time. Additionally, AEPB treatment upregulated the expression of growth hormone-1 (GH-1), insulin-like growth factor-1 (IGF-1), growth hormone receptor-1 (GHR-1), and cholecystokinin-a (CCKA) in zebrafish. Similarly, AEPB stimulated the expression and release of IGF-1 and accelerated mTOR expression in MC3T3-E1 cells. In addition, rapamycin hindered AEPB-induced linear growth in zebrafish larvae and suppressed the expression of growth-promoting genes by inhibiting mTOR activation. Conclusions: AEPB shows growth-promoting effects by upregulating growth-related genes and activating the mTOR signaling pathway. Further investigations are warranted to elucidate its mechanisms of action and explore its potential application in the development of growth-enhancing supplements for various purposes.

359-368

Authors: Wang, Zhou-Ting; Tang, Yue-Wen; Wan, Feng; Yang, Ru-Chun; Guo, Yan; Zheng, Jie; Li, You-Gui; He, Wei-Ming

Objective: To comparatively investigate the ameliorative effect of Phellinus igniarius (P. igniarius) on renal aging in a rat model of focal and segmental glomerulosclerosis (FSGS). Methods: The FSGS model was established in rats by uninephrectomy combined with tail vein injection of doxorubicin. The FSGS rats were randomly divided into the model group, the P. igniarius decoction group, the P. igniarius polysaccharides group, and the P. igniarius polyphenols group. Molecular indicators of cell senescence, renal function indexes, and podocyte injury markers were tested after ten weeks of intragastric administration. Besides, the pathological renal lesions and the ultrastructural changes were observed. Results: FSGS developed in the model group within ten weeks and showed segmental glomerular scarring and renal aging. Following the 10-week intervention, 24 h proteinuria, serum creatinine, blood urea nitrogen, P16INK4α, thrombospondin-1, and transforming growth factor-β1 were decreased in each treatment group, whereas albumin, erythropoietin, nephrin, and podocin were increased; the pathological renal injury was alleviated, and the number of senescent cells was reduced, especially in rats treated with P. igniarius decoction. Conclusions: P. igniarius ameliorates renal aging and renal injury in the FSGS rat model. Compared with the effective constituents (polysaccharides and polyphenols), P. igniarius decoction has a better curative effect, which is expected to provide a new therapeutic idea for FSGS.

287-295

Authors: Yucinda YY Khor, Siew-Keah Lee, M Dharmani Devi, Wei Chih Ling

Objective: To investigate the effect of epigallocatechin-3-gallate (EGCG) on endothelial dysfunction in spontaneously hypertensive rats (SHR). Methods: Wistar-Kyoto (WKY) rats and SHR were divided into four groups; WKY control, SHR control and SHR treated with EGCG (50 mg/kg/day) or losartan (10 mg/kg/day). The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days. Acetylcholine-induced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment. The vascular levels of reactive oxygen species, nitric oxide, tetrahydrobiopterin, and cyclic guanosine monophosphate were also measured. Moreover, the expression of angiotensin II type 1 (AT1) receptor protein was determined. Results: The systolic blood pressure was significantly decreased in SHR treated with EGCG. The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group. EGCG also significantly increased the levels of nitric oxide, tetrahydrobiopterin, and cyclic guanosine monophosphate, while decreasing the level of reactive oxygen species and the protein expression of AT1 receptor in SHR. Conclusions: EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability, which may be modulated partly by inhibition of vascular AT1 receptors. An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

306-314

Authors: Ya-Nan Shi, Jin-Zhu Su, Juan Wang, Jiang-Qiao Geng

Objective: To evaluate the effect of myricetin on ovalbumin (OVA)-induced allergic rhinitis in mice. Methods: Mice were sensitized and challenged using OVA (5%, 500 mL) intraperitoneally and intranasally, respectively, on an alternative day for 14 days, followed by administration of myricetin (50, 100, and 200 mg/kg) till day 21. Nasal symptoms, biochemical parameters, protein expressions, and histopathology were observed. Results: OVA-induced increased nasal symptoms including rubbing, sneezing, and discharge were significantly reduced by myricetin (100 and 200 mg/kg) (P<0.05). Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E (IgE; total and OVA-specific), total IgG1, and β-hexosaminidase levels, as well as leukotriene C4 and interleukins levels in nasal lavage fluid (P<0.05). Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells, while downregulating the protein expression of GATA binding protein 3, NF-κB, and 1κВ-α (P<0.05). Additionally, OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment (P<0.05). Conclusions: Myricetin exerts anti-allergic effects against OVA-induced allergic rhinitis via regulating Th1/Th2 balance.

242-249

Authors: Yosra Raziani, Kimia Karami, Hamid Reza Mohammadi, Hossein Mahmoudvand, Mohammad Nabi Moradi, Javad Ghasemian Yadegari

Objective: To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats. Methods: In order to induce diabetes, rats intraperitoneally received streptozotocin at 65 mg/kg. Sixty adult male Wistar rats were allocated into six groups (10 rats per each) including the healthy control group, the diabetic group as well as the diabetic group treated with Astragalus adscendens methanolic extract at 50, 100, and 200 mg/kg per day or glibenclamide (0.6 mg/kg/day) for 28 d. The effects of Astragalus adscendens methanolic extract on the levels of glucose, insulin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, urea, uric acid, total protein, albumin, triglyceride, cholesterol, α-amylase, oxidant/antioxidant enzymes, and inflammatory cytokines were evaluated. Real time-PCR was also used for measuring the gene expression of caspase-3, Bcl2, and Bax. Results: The levels of glucose, cholesterol, triglyceride, creatinine, urea, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and malondialdehyde considerably declined (P<0.001) in diabetic rats after treatment with Astragalus adscendens methanolic extract especially at a dose of 200 mg/kg. In addition, treatment with Astragalus adscendens methanolic extract noticeably increased the level of insulin, total protein, and albumin as well as improved the activities of catalase, glutathione peroxidase, and superoxide dismutase, as well as the expression levels of TNF-α, IL-1β, caspase-3, Bcl2 and Bax (P<0.001) compared to the diabetic control group. The extract also inhibited α-amylase in a dose-dependent manner with an IC50 value of 19.6 µg/mL. Conclusions: Astragalus adscendens methanolic extract shows potent antidiabetic, anti-inflammatory, anti-apoptotic, and antioxidant effects in diabetic rats. However, more studies are needed to verify the underlying mechanism of the effect of this plant extract and test its efficacy in clinical trials.

258-267

Authors: Thi Thanh Huong Le, Phu Hung Nguyen, Van Phuong Nguyen, Thy Ngoc Nguyen

Objective: To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell (CSC) number in gastric cancer. Methods: The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-adherent culture (3D) model was used to evaluate the effect of the extract on tumorsphere size and number. Moreover, the expression of CD44, ALDH, and p21 was determined by immunofluorescence analysis. Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH. Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes. Results: Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC50 of 55.7 µg/mL in MKN45 cells and 123.6 µg/mL in MKN74 cells. The extract also arrested cell cycle in the G0/G1 phase as well as significantly reduced the size and number of tumorspheres. The markedly increased expression of p21 was observed at both mRNA and protein levels in the extract-treated adherent cells and tumorspheres. In addition, Ardisia gigantifolia extract significantly reduced the number of CD44- and/or ALDH-expressing gastric CSC. Conclusions: The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.

195-204

Authors: Vineet Mehta, Priyanka Nagu, Arun Parashar, Manjusha Chaudhary

Objective: To explore the effect of Cassia fistula on collagen II-induced arthritis in rats. Methods: The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagen II-induced arthritis was investigated by evaluating paw volume, arthritis index, spleen index, and biochemical parameters. Histopathological analysis and docking study were also performed. Results: A dose-dependent reduction in paw volume, arthritic index, and spleen index was observed following oral administration of the chloroform and hydroalcoholic extracts. Treatment with Cassia fistula extracts reduced tumor necrosis factor-α, interleukin (IL)-1β, IL-6, prostaglandin E2, aspartate aminotransferase, alanine aminotransferase, total leucocyte count, and erythrocyte sedimentation rate while increasing IL-10 level. In addition, Cassia fistula extracts improved joint architecture, and prevented cartilage and bone destruction. Docking analysis demonstrated that the physcion, 1-octacosanol, 5,3',4'-trihydroxy-6-methoxy-7-O-α-L-rhamnopyranosyl-(1,2)-O-β-D-galactopyranoside and scopoletin may be responsible for the anti-arthritic effect of Cassia fistula. Conclusions: Cassia fistula suppresses the progression of collagen II-induced arthritis by lowering the inflammatory factors, decreasing paw volume and arthritic index, and alleviating joint architecture. However, further studies are required to confirm the bioactive molecule responsible for the anti-arthritic potential of Cassia fistula.

214-221

Authors: Xuan-Hai Do, Trong Nghia Nguyen, Thanh Chung Dang, Thi Thanh Mai Nguyen, Trung Nhan Nguyen, Van Nhat Truong Do, Huu Tho Le, Xuan Hai Nguyen, Hoang Phu Dang, Giang-Linh Nguyen, Dinh-Khanh Hoang, Van-Quan Le, Van-Mao Can

Objective: To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund's adjuvant-induced arthritis rat models. Methods: We isolated and identified five compounds in the ethanol-soluble Solanum procumbens extract (SP) with anti-inflammatory effects, including ursolic acid, β-sitosterol, hexadecanoic acid, cis-vaccenic acid, and vanillic acid. Additionally, we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms, including paw volumes, local temperatures, withdrawal latency, and mechanical withdrawal threshold at the hind paw and white blood cell (WBC) number from complete Freund's adjuvant-induced arthritis rat models. Results: We have successfully established a complete Freund's adjuvant-induced arthritis rat model at a low dose (1 mg/mL). SP extract significantly reduced paw volumes (P<0.05), prolonged withdrawal latencies (P<0.05), decreased local temperature, and increased the mechanical withdrawal threshold (P<0.05), but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers. Conclusions: SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis, but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.