The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy.

BACKGROUND: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. METHOD: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts' anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. RESULTS: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.

Natural Products as Novel Neuroprotective Agents; Computational Predictions of the Molecular Targets, ADME Properties, and Safety Profile.

Neurodegenerative diseases (NDs) are one of the most challenging public health issues. Despite tremendous advances in our understanding of NDs, little progress has been made in establishing effective treatments. Natural products may have enormous potential in preventing and treating NDs by targeting microglia; yet, there have been several clinical concerns about their usage, primarily due to a lack of scientific evidence for their efficacy, molecular targets, physicochemical properties, and safety. To solve this problem, the secondary bioactive metabolites derived from neuroprotective medicinal plants were identified and selected for computational predictions for anti-inflammatory activity, possible molecular targets, physicochemical properties, and safety evaluation using PASS online, Molinspiration, SwissADME, and ProTox-II, respectively. Most of the phytochemicals were active as anti-inflammatory agents as predicted using the PASS online webserver. Moreover, the molecular target predictions for some phytochemicals were similar to the reported experimental targets. Moreover, the phytochemicals that did not violate important physicochemical properties, including blood-brain barrier penetration, GI absorption, molecular weight, and lipophilicity, were selected for further safety evaluation. After screening 54 neuroprotective phytochemicals, our findings suggest that Aromatic-turmerone, Apocynin, and Matrine are the most promising compounds that could be considered when designing novel neuroprotective agents to treat neurodegenerative diseases via modulating microglial polarization.

Novel Anti-Tubulin Compounds from Trigonella foenum-graecum Seeds; Insights into In-vitro and Molecular Docking Studies.

BACKGROUND: Fenugreek, also known as Trigonella foenum-graecum L, is a natural plant that belongs to the Fabaceae family and has been known as a promising source of bioactive compounds. It has been widely used as traditional medicine since it has shown to lower blood glucose, manage cholesterol levels and further aid in the prevention and treatment of cancer. Herein, we aim to evaluate the anticancer activity of methanolic fenugreek seed extract against several cancer cell lines. METHODS: We sought to investigate the phytochemical classes present in multiple fenugreek seeds extracts using HPLC-DAD followed by LC/MS, predict and investigate anticancer activity using PASS online webserver, the CellTiter-Glo assay, evaluate ADME properties, and perform molecular docking for all bioactive compounds via Maestro software. RESULTS: Multiple extracts exhibited distinct phytochemical classes that demonstrated different biological activities. Fenugreek methanolic extract contains flavonoid chemical class, which showed the highest anticancer activity against the HCT8 cell line of colorectal cancer (IC50 of 8.83 µg/mL), followed by KAIMRC1 breast cancer cell line (IC50 of 35.06 µg/mL), HL60 leukemia cell line (37.80 µg/mL), MDA-MB-231 breast cancer cell line (38.51 µg/mL), and lastly, HCT116 colorectal cancer cell line with IC50 of 56.03 µg/mL. In contrast, the chloroform extract was inactive. The molecular docking study for all the bioactive compounds suggested that flavonoids F6 (-9.713 and -12.132), F7 (-10.166 and -12.411), and F11 (-10.084 and -13.516) possess the highest docking scores through SP and XP scores, respectively. CONCLUSION: The obtained results confirm that the bioactive compounds present in fenugreek seeds exhibit anticancer activity against several cancer cells that can mediate via tubulin polymerization inhibition. Although our study has evaluated the anticancer potential of Trigonella foenum-graecum as a promising natural source for new anticancer agents, fenugreek biological activity needs further research and investigations on their mechanism of action and toxicity profile.