Background: The anti-cancer effect of the halophyte Arthrocnemum indicum, a member of Arthrocnemum family of salt-tolerant plants, was evaluated against colorectal cancer cell, CaCo2. However, the anti-cancer effect of another halophyte Arthrocnemum machrostachyum was not investigated yet. Herein, the anticancer effect of A. machrostachyum methanolic extract (AME) was evaluated against Ehrlich solid tumor (EST) in mice and the potential mechanism of action was also studied. Methods: Male Swiss albino mice (n = 28) were randomly divided into 4 groups (n = 7/group). Group 1 (negative control group); group 2 (EST) injected intramuscularly by 0.2 mL Ehrlich ascitic carcinoma (2 × 10 6 cells); and groups 3 and 4 injected intratumorally with AME (180 and 360 mg/kg body weight, respectively) at D12 trice weekly for 2 weeks. Gene expression, protein expression, DNA damage, and TNFa level in tumors were determined by real-time PCR, western blot, comet assay, and Elisa, respectively. Results: Treatment with AME induced anti-tumor effects against EST as indicated by 1) notable reduction in tumor size; 2) elevation in tissue necrosis and apoptosis, as confirmed histologically; 3) increased DNA fragmentation; 4) decreased expression of the apoptotic genes (p53, Bax and caspase 3), and increased expression of the antiapoptotic marker Bcl2; 5) significantly upregulated cell cycle regulatory genes Cdc2 and connexin26, and; 6) decreased TNFa levels in tumor tissues. Interestingly, a high dose of AME exhibited a more potent anti-tumor effect against EST. Conclusion: These findings indicate that AME has a potent antitumor effect against EST and could be used as an adjuvant to anticancer drugs to combat tumor, but after application of further confirmatory clinical trials.

Methotrexate (MTX) is a chemotherapeutic agent widely used to treat a variety of tumors. Nonetheless, MTX‐induced hippocampal neurotoxicity is a well‐defined dose‐limiting adverse effect that limits clinical utility. Proinflammatory cytokine production and oxidative stress are possible mechanisms for MTX‐induced neurotoxicity. Buspirone (BSP), a partial agonist of the 5‐HT1a receptor (5‐HT1aR), has emerged as an anxiolytic drug. BSP has been shown to possess antioxidant and anti‐inflammatory effects. The current study investigated BSP's potential anti‐inflammatory and antioxidant effects in attenuating MTX‐induced hippocampal toxicity. Rats received either BSP (1.5 mg/kg) orally for 10 days and MTX (20 mg/kg) i.p. on Day 5. BSP administration markedly protected hippocampal neurons from drastic degenerated neuronal changes induced by MTX. BSP significantly attenuated oxidative injury by downregulating Kelch‐like ECH‐associated protein 1 expression while potently elevating hippocampal Nrf2, heme oxygenase‐1, and peroxisome proliferator‐activated receptor expression. BSP dampened inflammation by reducing NO2−, tumor necrosis factor‐alpha, IL‐6, and interleukin 1 beta levels mediated by downregulating NF‐κB and neuronal nitric oxides synthase expression. Moreover, BSP potently counteracted hippocampal pyroptosis by downregulating NLRP3, ASC, and cleaved‐caspase‐1 proteins. Therefore, BSP may represent a promising approach to attenuate neurotoxicity in patients receiving MTX.

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