Polysaccharides from Annona muricata leaves protect against cisplatin‑induced cytotoxicity in macrophages by alleviating mitochondrial dysfunction

Abstract

cisplatin is a prominent chemotherapeutic agent that can induce significant damage to normal cells. Therefore, it is important to develop agents that protect normal cells without influencing the chemotherapeutic effect of cisplatin. The present study was conducted to explore the protective effects of Annona muricata leaf polysaccharides (ALPS) against cisplatin-induced toxicity in macrophages. Apoptosis was assessed in macrophages and lung cancer cells to investigate the cytoprotective effect of ALPS, their effect on the production of cisplatin-induced reactive oxygen species (ROS) and the loss of the mitochondrial transmembrane potential (MTP). Cisplatin, when used alone or in combination with ALPS, showed significant toxicity against A549 and H460 lung cancer cells. However, cisplatin-induced cytotoxicity was suppressed by cotreatment of RAW 264.7 macrophages with ALPS. ALPS significantly inhibited the upregulation of Bax, cytosolic cytochrome c and caspases-3, -8 and -9. Moreover, ALPS resulted in the cleavage of PARP and downregulation of Bcl-2 levels in a concentration-dependent manner, which ultimately led to a reduction in the apoptotic and necrotic populations of cisplatin-treated RAW 264.7 macrophages. The suppression of the apoptotic signaling pathways was mediated through the reduction of ROS and MTP loss in cisplatin-treated RAW 264.7 macrophages. In addition, ALPS alleviated cell damage by suppressing the mitochondrial apoptotic pathways in cisplatin-treated bone marrow-derived macrophages. Together, these findings suggested that ALPS may alleviate the toxic side effects of chemotherapeutic agents and act as a potential candidate for use as an effective adjuvant therapy.

Cell Viability Assessment by MTT After Treatment of Hepatocellular Carcinoma Cells (HepG2) with Chelidonium majus

“…14 The cytotoxicity of Chelidonium majus was also compared with Mahonia aquifolium and Canadian Sanguinaria, and the authors observed that Chelidonium majus exhibited higher cytotoxicity to melanoma cell lines compared to the other extracts. 15 Based on these findings, it is possible to observe that Chelidonium majus has confirmed antitumor action in different cell lines and induces apoptosis. This effect was observed in the present study since there was a decrease in the HepG2 cell viability after treatment with the homeopathic Chelidonium majus D35.…”

Biflavonoid quercetin protects against cyclophosphamide–induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity

“…Studies (9)(10)(11)(12)(13)(14)(15) have continued to support the opinion that a number plants and plant bioactive compounds posses (in addition to their antioxidant and antiinflammatory properties) significant anticancer activity in both in-vitro and in-vivo scenarios. Some flavonoids like curcumin and quercetin have also been reported to possess chemopreventive properties through their antioxidant properties; and ability to induce cell-cycle arrest, cell growth and apoptosis (16).There is also recent evidence of the antiproliferative effects of quercetin (either alone or in combination with other flavonoids) in different cancer models (17)(18)(19)(20).…”