Lippia javanica (Burm. F.) Herbal Tea: Modulation of Hepatoprotective Effects in Chang Liver Cells via Mitigation of Redox Imbalance and Modulation of Perturbed Metabolic Activities.

Introduction: Hepatic oxidative injury is one of the pathological mechanisms that significantly contributes to the development of several liver diseases. In the present study, the hepatoprotective effect of Lippia javanica herbal tea was investigated in Fe2+- mediated hepatic oxidative injury. Methods: Using an in vitro experimental approach, hepatic oxidative injury was induced by co-incubating 7 mM FeSO4 with Chang liver cells that have been pre-incubated with or without different concentrations (15-240 µg/mL) of L. javanica infusion. Gallic acid and ascorbic acid served as the standard antioxidants. Results: The infusion displayed a reducing antioxidant activity in ferric-reducing antioxidant power (FRAP) assay and a potent scavenging activity on 2,2-diphenyl-2- picrylhydrazyl (DPPH) radical. Pretreatment with L. javanica infusion significantly elevated the levels of reduced glutathione and non-protein thiol, and the activities of superoxide dismutase (SOD) and catalase, with concomitant decrease in hepatic malondialdehyde levels, acetylcholinesterase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase and lipase activities. The infusion showed the presence of phytoconstituents such as phenolic compounds, tannins, phenolic glycosides and terpenoids when subjected to liquid chromatography-mass spectrometry analysis. Molecular docking revealed a strong binding affinity of dihydroroseoside and obacunone with both SOD and catalase compared to other phytoconstituents. Conclusion: These results portray a potent antioxidant and hepatoprotective effect of L. javanica, which may support the local usage of the herbal tea as a prospective therapeutic agent for oxidative stress-related liver diseases.

Cannabis with breast cancer treatment: propitious or pernicious?

Cannabis has been used for various medicinal applications including, but not limited to, cancer: most commonly to treat chemotherapy-associated side effects. Cannabis is often used for its palliative effects in the form of purified cannabinoids, or as extracts. This study was conducted using two breast cancer cell lines and aimed to evaluate potential anti-proliferative "intra-entourage effects" between purified phytocannabinoids resembling the THC and CBD ratios of medicinal and recreational cannabis strains, as well as to investigate potential "inter-entourage effects" between the different ratios and the phytochemicals found in a Cannabis sativa extract. This study also aimed to evaluate the potential interaction between cannabinoids and chemotherapeutic agents. The data identified an intra-entourage effect present in the MCF-7 cells when treated with a recreational, but not a medicinal, cannabis formulation. This effect may be due to THC partially exerting its anti-proliferative effects through the estrogen receptor (ER), present in the MCF-7 cell line. Little to no intra-entourage effects were observed in the MDA-MB-231 cell line and no inter-entourage effects were observed in either cell line. The simultaneous treatment of the MCF-7 cell line with various cannabinoid formulations and the common breast cancer treatment, tamoxifen, resulted in the diminished anti-proliferative activity of tamoxifen, an effect that was more evident when combined with recreational cannabis formulations. Since cannabis is commonly used in palliative care to treat chemotherapy-associated side effects, further research is required to investigate the potential interference of various cannabis formulations to ensure that the efficacy of chemotherapeutic agents is not compromised. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03102-1.

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells.

This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis. The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis. Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed. The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.