Integration of phytotherapy and chemotherapy: Recent advances in anticancer molecular pathways.

Cancer is a disease characterized by abnormal and uncontrolled growth of cells, leading to invasion and metastasis to other tissues. Chemotherapy drugs are some of the primary treatments for cancer, which could detrimentally affect the cancer cells by various molecular mechanisms like apoptosis and cell cycle arrest. These treatment lines have always aligned with side effects and drug resistance. Due to their anticancer effects, medicinal herbs and their active derivative compounds are being profoundly used as complementary treatments for cancer. Many studies have shown that herbal ingredients exert antitumor activities and immune-modulation effects and have fewer side effects. On the other hand, combining phytotherapy and chemotherapy, with their synergistic effects, has gained much attention across the medical community. This review article discussed the therapeutic effects of essential herbal active ingredients combined with chemotherapeutic drugs in cancer therapy. To write this article, PubMed and Scopus database were searched with the keywords "Cancer," "Combination," "Herbal," "Traditional," and "Natural." After applying inclusion/exclusion criteria, 110 articles were considered. The study shows the anticancer effects of the active herbal ingredients by inducing apoptosis and cell cycle arrest in cancer cells, especially with a chemotherapeutic agent. This study also indicates that herbal compounds can reduce side effects and dosage, potentiate anticancer responses, and sensitize cancer cells to chemotherapy drugs.

Synergistic apoptotic effects of ethanolic extracts of ginger and Ganoderma lucidum in a colorectal cancer cell line.

Current conventional therapy for colorectal cancer includes surgery, radiation and chemotherapy, all of which produce side effects. Herbal medicine can control the side effects of conventional treatments. We investigated the synergistic effect of a mixture of Zingiber officinale Roscoe (Ginger) and Ganoderma lucidum extracts on colorectal cancer cell apoptosis in vitro. We prepared ethanolic extracts of ginger (GEE) and G. lucidum (GLEE). Cytotoxicity was evaluated using MTT assay and the half-maximal inhibitory concentration (IC50) of each extract was calculated. The effect of these extracts on apoptosis in cancer cells was assessed using flow cytometry; Bax, Bcl2 and caspase-3 gene expression was evaluated using real-time PCR. GEE and GLEE decreased CT-26 cell viability significantly in a dose-dependent manner; however, the combined application of GEE + GLEE was most effective. Bax:Bcl-2 gene expression ratio, caspase-3 gene expression and the number of apoptotic cells were increased significantly in CT-26 cells treated at the IC50 level of each compound, especially in the GEE + GLEE treatment group. Combined ginger and Ganoderma lucidum extracts exhibited synergistic antiproliferative and apoptotic effects on colorectal cancer cells.

Evaluation of Tcell exhaustion based on the expression of EOMES, Tbet and co-inhibitory receptors in severe and non-severe covid-19 patients.

During viral infections, especially Covid-19, Tcell exhaustion plays a crucial role in reducing the activity of lymphocytes and the immune system's antiviral activities. This research aimed to investigate the co-inhibitory receptors and transcription factors involved in the Tcell exhaustion process in ICU-admitted (ICUA) compared to non-ICU admitted (non-ICUA) Covid-19 patients. A total of 60 Covid-19 patients (30 patients in the severe group who were admitted in the ICU (ICUA) and 30 patients in the mild group who were admitted in departments other than the ICU (non-ICUA)) and 10 healthy individuals were included in this study. Laboratory tests and the level of gene expressions related to 4 inhibitory co-receptors, including LAG-3, TIM-3, TIGIT, PD-1, and T-bet and Eomes transcription factors involved in the process of Tcell exhaustion in severe and mild patients of Covid-19 were investigated. The results showed lymphopenia and an increase in other hematologic laboratory factors such as NLR, PLR, CRP, ALT, and AST in people with a severe form of the disease (ICUA) compared to mild groups (non-ICUA) (P < 0.001). Furthermore, a significant increase in 3 co-inhibitory receptors, TIM-3, LAG-3, and PD-1, was observed in severe patients compared to mild and healthy people (P < 0.001). An increase in TIGIT gene expression was lesser than the other three mentioned receptors (P < 0.05). Concerning the transcription factors, we observed a significant increase in Eomes in ICUA patients compared to the non-ICUA group (P < 0.001), and this increment in T-bet gene expression was minor compared to Eomes (P < 0.05). In conclusion, Patients with a severe form of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represented a higher level of gene expressions in terms of co-inhibitory receptors and transcription factors involved in the T cell exhaustion process.

The immune system's role in PCOS.

Polycystic ovary syndrome (PCOS) is a common disorder of the endocrine system. Its main manifestations include oligo-ovulation, hyperandrogenism, and polycystic ovary morphology (PCOM), affecting women of childbearing age. Although the exact pathogenesis of this disease is still unknown, many factors, including genetic, endocrine, and metabolism disorders, play critical roles in its development. The immunopathogenesis of PCOS has not yet been studied in-depth, but it is hypothesized that immune system abnormalities may play a key role in it. Recent research has shown inflammation's effect on ovulation and ovarian follicular dynamics. Thus, it is suggested that there is a close association between PCOS and low-grade chronic systemic inflammation. As a result, chronic low-grade inflammation is identified as a significant factor in the pathogenesis and development of PCOS, which in turn leads to infertility. As a result, this article reviews PCOS immunopathology, evaluates long-standing hypotheses about the immune system's role in PCOS, and assesses the association between inflammatory factors and PCOS.

Protective Effects of Curcumin against Lipopolysaccharide-Induced Toxicity.

BACKGROUND: Lipopolysaccharide (LPS), a Gram-negative bacterial cell wall component, evokes intensive inflammatory responses in the human body. Naturally, inflammation is a part of the host immune response to an infection; nonetheless, an exaggerated response can lead to a series of pathophysiological consequences, collectively known as LPS toxicity or septic shock. OBJECTIVE: This review will explore the cellular and experimental investigations that mainly focus on Curcumin's therapeutic effects on the LPS-mediated inflammatory responses. METHOD: A literature review of all relevant studies was performed. CONCLUSION: Curcumin has been reported to exert anti-inflammatory properties by interfering with LPS-induced inflammatory pathways, including binding to cell surface receptors of LPS, NF-kB activation pathway, and inflammasome activation. Further clinical studies on the effect of Curcumin in reducing the pathophysiological consequences of LPS toxicity would substantiate the use of this molecule for future therapeutic approaches.

Macrophage polarization by phytotherapy in the tumor microenvironment.

Several signaling pathways were involved in M1 (classic) and M2 (alternative) macrophage polarization. Disruption of M2-related signaling pathways and improvement of M1-related signaling pathways can be identified as one of the cancer therapeutic approaches. Prevention of macrophage differentiation into M2 by different herbal agents with antitumor properties can be considered as a promising therapeutic target for cancer patients. In the present review study, we investigated the effect of herbal compounds on M1 and M2 related signaling pathways to reduce M2 and increase M1 macrophage polarization for the treatment of different types of cancer.

Synergistic Evaluation of Ginger and Licorice Extracts in a Mouse Model of Colorectal Cancer.

Herbal medicine can be used to overcome the side effects of conventional treatments. This study aimed to evaluate the anticancer activities of ginger and licorice extracts, as well as the synergistic effects of their combination. Ginger ethanolic extract (GEE) and licorice methanolic extract (LME) were isolated by a Soxhlet extractor. Next, the anti-proliferative activity of the extracts, apoptosis induction, tumor growth inhibition, and tumor-infiltrating T lymphocytes were investigated. The MTT (3-[4, 5-dimethylthiazol-2-yl]-2, five diphenyl tetrazolium bromide) assay showed that GEE and LME decreased the CT26 cell viability in a dose-dependent manner; however, the GEE + LME combination was more effective (P < 0.05). The CT26 cells treated with each extract showed a significant increase in Bax/Bcl-2 ratio and caspase-3 gene expression, especially in the GEE + LME group (P < 0.001). Tumor volume significantly reduced in the GEE + LME group, compared to the negative controls. Finally, mice treated with GEE + LME showed a significant increase in the CTL/Treg cell ratio (P < 0.001) and Bax/Bcl2 ratio (P < 0.05). The study results revealed that GEE + LME can suppress cancer cell growth, increase apoptosis, and improve CTL infiltrating to the tumor site in a synergetic manner in-vivo and in-vitro. Therefore, the prepared mixture can be used in future clinical trials.