Hormone-sensitive lipase (HSL) is a pivotal enzyme that mediates triglyceride hydrolysis to provide free fatty acids and glycerol in adipocytes in a hormonally controlled lipolysis process. Elevated plasma-free fatty acids were accompanied by insulin resistance, type-2 diabetes, and obesity. Inhibition of lipolysis through HSL inhibition may provide a mechanism to prevent the accumulation of free fatty acids and to improve the affectability of insulin and blood glucose handling in type II diabetes. The published studies that examine the structure, regulation, and function of HSL and major inhibitors were reviewed in this paper.

Mitochondrial complex V (ATP synthase) is a remarkable molecular motor crucial in generating ATP and sustaining mitochondrial function. Its importance in cellular metabolism cannot be overstated, as malfunction of ATP synthase has been linked to various pathological conditions. Both natural and synthetic ATP synthase inhibitors have been extensively studied, revealing their inhibitory sites and modes of action. These findings have opened exciting avenues for developing new therapeutics and discovering new pesticides and herbicides to safeguard global food supplies. However, it is essential to remember that these compounds can also adversely affect human and animal health, impacting vital organs such as the nervous system, heart, and kidneys. This review aims to provide a comprehensive overview of mitochondrial ATP synthase, its structural and functional features, and the most common inhibitors and their potential toxicities.

Context: Recent scientific studies have reported that essential oils induce apoptosis in various cancer cell types by interfering with intracellular signaling pathways. Aims: To evaluate the cytotoxicity, the apoptotic activity of essential oil (EO) of Ruta chalepensis L. against MCF-7 cell line. Methods: Cytotoxicity was determined using methyl thiazol tetrazolium assay. The apoptotic activity of EO was analyzed using annexin V-fluorescein isothiocyanate/propidium iodide binding flow cytometry. The cell morphology was inspected under an inverted microscope. DAPI staining assay was used for the morphological observation. Activation of caspases-3/7, -8, and-9 was assessed using a caspase assay kit. Results: Ruta chalepensis essential oil significantly inhibited the proliferation of MCF-7 cells at 72 h. Moreover, the results showed that cell death is associated with the apoptotic process, and the number of apoptotic cells was significantly increased in the groups treated with EO than in control cells. The main morphological hallmarks of apoptosis in the nucleus were membrane blebbing, chromatin condensation, and nuclear fragmentation. Also, R. chalepensis EO-induced apoptosis in the MCF-7 cell line was via the extrinsic caspase-8 dependent pathway in a dose and time-dependent manner. Conclusions: Ruta chalepensis essential oil demonstrated significant apoptotic activity against experimental breast carcinoma. Therefore, it could be introduced as a suitable candidate for breast cancer therapy after further investigation.

Context: Ajuga orientalis L. (Lamiaceae) is an aromatic herb used in traditional medicine in Jordan and neighboring countries. Aims: To evaluate the cytotoxic potential of ethanolic and aqueous extracts from the aerial parts of A. orientalis against three cell lines MCF-7, Caco-2, and HDFa. In addition to assessing the total phenolic and flavonoid contents, antioxidant activity. Further to analyze the phytochemical constituents. Methods: The phytochemical analysis was performed using gas chromatography/mass spectrometry. The total phenolic (TPC) and flavonoid (TFC) contents were assessed using colorimetric methods. The antioxidant properties of both extracts were assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reducing power ability. Cytotoxicity was investigated using methyl thiazol tetrazolium (MTT) assay. Results: The most abundant compounds in the extract were 9-octadecenoic acid, methyl ester, (E)- (27.2%), hexadecanoic acid, methyl ester (12.8%), and methyl stearate (9.6%). The ethanolic extract demonstrated higher TPC and TFC than the aqueous extract. Also, the ethanolic extract showed higher antioxidant activity than aqueous extract using DPPH and the reducing power ability. Furthermore, the aqueous extract of A. orientalis has a potent cytotoxic effect against the Caco-2 cell line (IC50 = 2.059 ± 0.10 μg/mL). In contrast, the ethanolic extract demonstrated a cytotoxic effect against the MCF-7 cell line (IC50 = 59.32 ± 0.04 μg/mL). Both extracts did not exhibit a toxic effect against normal dermal fibroblast cell line (HDFa). Compared to non-cancerous cells, the ethanolic extract of A. orientalis demonstrated high selectivity against MCF-7 cells and limited selectivity against Caco-2 cells. In comparison, the aqueous extract was highly selective against both cancerous cells. Conclusions: A. orientalis demonstrated antioxidant properties and significant antiproliferative potential against breast and colon cancer. Therefore, additional investigations are needed to study the mechanism of the cytotoxicity for this plant.

Calaminthaincana, a medicinal plant traditionally used for its therapeutic properties, has been investigated for its phytochemical constituents and biological activities. Through a specific LC‐MS/MS analysis method, the phytochemical constituents of Calamintha incana methanolic extract have been identified and quantified. The 2,2‐diphenyl‐1‐picrylhydrazyl method was used to measure the antioxidant properties. The antibacterial properties of this extract have been tested against four harmful bacteria using disc diffusion and the minimum inhibitory concentration methods. A colorimetric assay has evaluated the total phenolic and flavonoid content. The extract contained 34 compounds, with linolenic acid (11.2%) and myristic acid (10.3%) being the most abundant. Despite the low phenolic and flavonoid content, the extract exhibited antioxidant activity with an IC₅₀ of 96.8 ± 0.3 μg/mL. Moreover, the extract demonstrated potent antimicrobial properties against B. cereus and S. aureus, with minimum inhibitory concentrations of 11.8 and 21.5 μg/mL, respectively. These robust results underscore the potential of C. incana methanolic extract in the development of effective antibacterial agents.

This study aimed to assess the antioxidant and antidiabetic properties of ethanolic phytoextracts of Calamintha incana (Sm.) Helder leaves. Initially, the chemical characterization of the phytocomplex was performed using high-performance liquid chromatography (HPLC)/mass spectrometry (MS). The cytotoxicity of the ethanolic extract was assessed using an MTT assay in HepG2 cells. Subsequently, antioxidant activity was evaluated using a DPPH test. Finally, enzymatic tests with α-amylase, α-glucosidase, pancreatic lipase, and dipeptidyl peptidase IV (DPP-IV) were performed to evaluate their effects on glucose metabolism. The chemical composition of the extract is p-linolenic acid (13.2%), myristic acid (12.1%), and p-cymene (10.5%). The extract demonstrated low toxicity, with none of the tested concentrations inducing 50% cell death. Furthermore, the ethanolic extract revealed potent antioxidant activity using DPPH (IC₅₀ was 35.9 ± 0.7 µg/mL) and reducing power capacity (IC₅₀ was 90.3 ± 0.8 µg/mL). Regarding the antidiabetic activity, the extract caused a significant inhibition of α-amylase, α-glucosidase (IC₅₀ 46.3 ± 0.2, 56.8 ± 0.1 μg/mL, respectively), weak inhibition of pancreatic lipase and no notable inhibition of dipeptidyl peptidase IV. In conclusion, C. incana has antioxidant and antidiabetic properties and appears to exert insulin-independent hypoglycemic action.