Asian Pacific Journal of Tropical Biomedicine

523-531

Authors: Xiu-Mei Bo, Ruo-Bing Yu, Sai-Jun Du, Rong-Li Zhang, Ling He

Objective: To identify the anti-depressive effect of ferulic acid (FA) in mice exposed to lipopolysaccharide (LPS) and explore its molecular mechanisms. Methods: The mice were divided into 5 groups as follows: Control, LPS, LPS + SP, LPS + FA, and LPS + FA + anisomycin. The LPS + FA and LPS + FA + anisomycin groups were administered with FA (100 mg/kg, i.p.) once daily continuously for 7 days, and the other groups received an equivalent volume of saline. On the 7th day, LPS (0.1 mg/mL, i.p.) was injected in all mice except the control group 30 min after FA or saline administration. The LPS + SP and LPS + FA + anisomycin groups were intravenously administered with SP600125 [c-Jun N-terminal kinase (JNK) inhibitor] (100 μL/ site, i.v.) and anisomycin (JNK activator) (100 μL/site, i.v.) 15 min before LPS, respectively. The depressive behaviors were assessed by open field test, sucrose preference test, and forced swimming test at 24 h post-LPS administration. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in plasma were measured by ELISA. The levels of phospho-JNK, TNF-α, IL-1β, Bcl-2, Bax, cytochrome c and caspase-3 were evaluated by Western blotting. Results: FA alleviated depression symptoms caused by LPS in mice, including increasing sucrose water consumption in sucrose preference test and reducing the immobility time in forced swimming test. FA could inhibit upregulated levels of phospho-JNK, TNF-α, and IL-1β. FA also markedly decreased Bax, caspase-3, and cytochrome c, and increased Bcl-2 levels. Besides, SP600125 showed neuroprotective effect similar to FA which was attenuated by anisomycin. Conclusions: FA attenuates inflammation and apoptosis by inhibiting LPS-induced activation of JNK to alleviate depressionlike behaviors.

540-546

Authors: Shaza A Alyamani, Mayson H Alkhatib, Faiza Abdu

Objective: To evaluate the protective effect of the coconut oil nanoemulsion against methotrexate-induced hepatotoxicity and nephrotoxicity in Ehrlich ascites carcinoma-bearing Swiss albino mice. Methods: Forty mice were divided into four groups. Group I served as the untreated Ehrlich ascites carcinoma-bearing mice while Ehrlich ascites carcinoma-bearing mice in groups II-IV received an intraperitoneal injection of 0.2 mL/kg coconut oil nanoemulsion, 20 mg/kg methotrexate as well as 0.2 mL/kg coconut oil nanoemulsion mixed with 20 mg/kg methotrexate, respectively. The toxicities of the treatments were assessed by determining the complete blood count, performing the serum analysis for liver and kidney functions, evaluating the oxidative status and visualizing histological changes in the liver and kidney tissues. Results: Treatment with methotrexate and coconut oil nanoemulsion markedly diminished the liver parameters including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, direct bilirubin and total bilirubin which were raised by methotrexate treatment (P < 0.05). Similarly, creatinine and blood urea nitrogen, as the indicators of kidney function, were dramatically lowered in the combination treatment group compared to the methotrexate group (P < 0.05). In addition, treatment with methotrexate and coconut oil nanoemulsion reduced the malondialdehyde and increased catalase, glutathione reductase and superoxide dismutase, in the liver and kidney tissues (P < 0.05). The treatment with methotrexate and coconut oil nanoemulsion reduced white blood cell count and increased the hemoglobin amount (P < 0.05), but did not cause any change in platelets and red blood cell count. Conclusions: Coconut oil nanoemulsion as a nanocarrier has great potential in reducing the adverse side effects induced by methotrexate.

555-562

Authors: Md. Nazim Uddin, Md. Abdus Samad, Md. Abu Zubair, Md. Zahurul Haque, Kanika Mitra, Tanzir Ahmed Khan, Md Amir Hossain, Ashikujaman Syed, Aklima Afroze

Objective: To investigate bioactive phytochemicals and antioxidant activities of Nymphaea nouchali and to explore its anticancer pathways by a network pharmacology approach. Methods: Using a spectrophotometer and high-performance liquid chromatography-diode array detector (HPLC-DAD), we quantified bioactive phytochemicals in methanolic extract of Nymphaea nouchali tuber. The extracts were investigated for in vitro antioxidant properties. Targets of these bioactive phytochemicals were predicted and anticancer-associated pathways were analyzed by a network pharmacology approach. Moreover, we identified the predicted genes associated with cancer pathways and the hub genes in the protein-protein interaction network of predicted genes. Results: Quantitative results indicated the total phenolics, total flavonoids, and total proanthocyanidins in the methanolic extract of Nymphaea nouchali tuber. HPLC-DAD analysis showed rutin (39.44 mg), catechin (39.20 mg), myricetin (30.77 mg), ellagic acid (11.05 mg), gallic acid (3.67 mg), vanillic acid (0.75 mg), rosmarinic acid (4.81 mg), p-coumaric acid (3.35 mg), and quercetin (0.90 mg) in 1 g of dry extract. The extract showed the radical scavenging activities of 2, 2-diphenyl-1-picrylhydrazyl, 2,2’-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) and N,N-dimethyl-p phenylenediamine. By using network pharmacology, we predicted 130 target genes associated with cancer pathways. The top hub genes (IL6, AKT1, EGFR, JUN, PTGS2, MAPK3, CASP3, and CXCL8) were also identified, which were associated with cancer pathways and interacted with bioactive phytochemicals of the methanolic extract of Nymphaea nouchali tuber. Conclusions: Our study provides insights into the mechanism of anticancer activities of the methanolic extract of Nymphaea nouchali tuber.