Objective: To evaluate the effect of the ethyl acetate fraction derived from Sargassum pallidum extract against particulate matter (PM)-induced oxidative stress and inflammation in HaCaT cells and zebrafish. Methods: HaCaT cells and zebrafish were used to evaluate the protective effects of the ethyl acetate fraction of Sargassum pallidum extract against PM-induced oxidative stress and inflammation. The production of nitric oxide (NO), intracellular ROS, prostaglandin E2 (PGE2), and pro-inflammatory cytokines, and the expression levels of COX-2, iNOS, and NF-κB were evaluated in PM-induced HaCaT cells. Furthermore, the levels of ROS, NO, and lipid peroxidation were assessed in the PM-exposed zebrafish model. Results: The ethyl acetate fraction of Sargassum pallidum extract significantly decreased the production of NO, intracellular ROS, and PGE2 in PM-induced HaCaT cells. In addition, the fraction markedly suppressed the levels of pro-inflammatory cytokines and inhibited the expression levels of COX-2, iNOS, and NF-κB. Furthermore, it displayed remarkable protective effects against PM-induced inflammatory response and oxidative stress, represented by the reduction of NO, ROS, and lipid peroxidation in zebrafish. Conclusions: The ethyl acetate fraction of Sargassum pallidum extract exhibits a protective effect against PM-induced oxidative stress and inflammation both in vitro and in vivo and has the potential as a candidate for the development of pharmaceutical and cosmeceutical products.

Objective: To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis rats. Methods: Colitis was induced by intracolonic administration of acetic acid solution (4% v/v) in rats. Rats were divided into six groups including the sham group, the negative control group, the dexamethasone-treated group, and the groups treated with isoimperatorin (0.1, 1, and 10 mg/kg/d by gavage). The treatments were administered for three days and then colonic status was assessed by macroscopic, histopathological, and biochemical analyses. Results: Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced colitis. It also significantly reduced myeloperoxidase, TNF-α, IL-1β, and malodialdehyde levels. Conclusions: Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

Objective: To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo. Methods: The effects of the methanolic extract of Ephedra alata on the viability, migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay, Transwell assay, and annexin V-FITC staining assay, respectively. Histological examination was also carried out. Moreover, a murine breast cancer model was established to evaluate the inhibitory effect of the extract. Biochemical parameters including hepatic and non-hepatic enzymes, malondialdehyde, and glutathione were investigated. Results: The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent manner. It also induced apoptosis in 4T1 cells. In an in vivo mouse model, the extract markedly inhibited tumor growth, reduced malondialdehyde, and hepatic and non-hepatic enzymes as well as increased glutathione level. Conclusions: The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo, which may be a promising anticancer agent.

Asian Pacific Journal of Tropical Biomedicine +Advanced Search Home About Authors Subscribe Contact Us Hainan Medical University Press Archive > Volume Issue 4 > 2024(4):162-169. DOI:10.4103/apjtb.apjtb_852_23 Prev Next Ellagic acid inhibits gastric cancer cells by modulating oxidative stress and inducing apoptosis Jian Zheng Chun-Feng Li Article Metrics Preview PDF Reference Abstract: Objective: To evaluate the anticancer effect of ellagic acid on gastric cancer cells. Methods: MTT assay was used to evaluate the effect of ellagic acid at different concentrations (0.5-100 μg/mL) on gastric cancer AGS cells. RT-qPCR and Western blot analyses were applied to assess apoptosis (BCL-2, CASP-3, and BAX) and autophagy (LC3, ATG5, and BECN1) in AGS cells treated with ellagic acid. The expression of invasion-related markers including TP53, CDKN2A, and PTEN was determined. In addition, cell cycle markers including cyclin A, B, D, and E were measured by ELISA. Oxidative stress markers were evaluated using spectrophotometry. Results: Ellagic acid inhibited the proliferation of AGS cells in a concentration- and time-dependent manner. The expression of BCL- 2 was significantly decreased (P<0.05) and CASP-3 and BAX were markedly increased (P<0.01) in AGS cells treated with ellagic acid. However, this compound induced no significant changes in the expression levels of LC3, ATG5, and BECN1 (P>0.05). Moreover, the oxidative stress markers including SOD, TAC, and MDA were increased by ellagic acid (P<0.01). Conclusions: Ellagic acid can inhibit cell proliferation, induce apoptosis, and modulate oxidative stress in AGS cells. However, further in vivo and molecular studies are needed to verify its anticancer efficacy.

Objective: To determine the inhibitory effects of pachymic acid on lung adenocarcinoma (LUAD) cells and elucidate its underlying mechanism. Methods: CCK-8, wound healing, Transwell, Western blot, tube formation, and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation, metastasis, angiogenesis as well as autophagy. Subsequently, molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B (PTP1B). Moreover, PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid. Results: Pachymic acid suppressed LUAD cell viability, metastasis as well as angiogenesis while inducing cell autophagy. It also targeted PTP1B and lowered PTP1B expression. However, PTP1B overexpression reversed the effects of pachymic acid on metastasis, angiogenesis, and autophagy as well as the expression of Wnt3a and β-catenin in LUAD cells. Conclusions: Pachymic acid inhibits metastasis and angiogenesis, and promotes autophagy in LUAD cells by modulating the Wnt/ β-catenin signaling pathway via targeting PTP1B.

Objective: To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo. Methods: Bioinformatic analysis was performed using atom pair fingerprints. An in vitro combination test was performed against Babesia bovis and Theileria equi. Moreover, the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay. Results: Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights. The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi. In addition, 5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment. The combination therapy also normalized the hematological parameters of infected mice. Conclusions: An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice, suggesting it might be a new paradigm for the treatment of babesiosis.

Objective: To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats. Methods: Rats were randomly divided into six groups: the control group, the asthmatic group, and the asthmatic groups treated with dexamethasone (1 mg/kg; oral gavage) or three doses of rosmarinic acid (0.5, 1, and 2 mg/kg; oral gavage). For induction of asthma, rats received intraperitoneal injections and inhalation of ovalbumin. After 21 days, bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses. Moreover, total and differential white blood cell counts were determined. Results: The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group. In addition, rosmarinic acid reduced white blood cell count and the percentages of eosinophils, monocytes, and neutrophils while increasing the percentage of lymphocytes. Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid. Conclusions: Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

Objective: To evaluate the effects of Capsosiphon fulvescens (C. fulvescens) ethanolic extract on inflammation in lipopolysaccharide (LPS)-induced RAW296.7 macrophages. Methods: The protective effects of C. fulvescens ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis, including enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis. To examine reactive oxygen species (ROS) production, flow cytometry analysis, and immunofluorescence staining were used. Furthermore, the modulatory effect of C. fulvescens ethanolic extract on NF-κB activation was investigated. Results: C. fulvescens ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix metalloproteinases. In addition, C. fulvescens ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling pathway. Conclusions: C. fulvescens ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 macrophages. C. fulvescens can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.