Ali E. Rasslan

The prevalence and comorbidity of psychiatric diseases such as depression are widespread. Depressive disorders, as one of the most common types of mental disorders, have a significant impact on both individuals and society. Depressive disorders are prevalent mental disorders. This causes 264 million people worldwide to suffer from depression. Different types of depression treatment are available, but current psychiatric drugs cause many side effects, such as sexual dysfunction, metabolic syndrome, dependency, and weight gain. Herbal medicines can somewhat solve this problem with minimal side effects. Herbs and herbal preparations are utilized on a large scale for the treatment of mental diseases, especially depression. For example, St. John's wort is effective for the treatment of mild-to-moderate depression. Scientific research supports the potential of ashwagandha to treat clinical depressive disorders. Studies show that its effects are comparable to common prescription antidepressants. Supplementation with Melissa can decrease depression, anxiety, stress, and sleep disorders in patients with central sleep apnea. Several clinical studies have demonstrated the benefit of lavender extracts in comparison to reference or placebo in decreasing symptoms of anxiety and depression. A clinical study found that chamomile was effective for severe depression.

Micromeria biflora is widely used traditionally for various disorders, such as wounds, nosebleeds, and sinusitis. The study was conducted to investigate the chemical and pharmacological properties of M. biflora aerial parts. Gas chromatography–mass spectrometry (GC–MS) analysis revealed the presence of 84 components in M. biflora total methanolic extract (MBTME). The toxicity study showed no morbidity and/or mortality at the tested concentrations. The estimated LD₅₀ value of MBTME was greater than 3 g/kg body weight. MBTME exhibited significant 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity and increased reducing power in the ferric reducing antioxidant power (FRAP) assay with the elevation in concentration. MBTME demonstrated significant anticancer efficacy against hepatocellular carcinoma (HepG‐2), colon carcinoma (HCT‐116), and intestinal carcinoma (Caco‐2) cell lines with IC₅₀ values of 23.14 ± 2.92, 28.22 ± 3.07, and 18.70 ± 3.36 µg/mL, respectively. Histological examination revealed substantial morphological changes consistent with the observation associated with the apoptotic mechanism of action. The molecular docking study provided insights into the rational binding modes of the identified compounds with poly(ADP‐ribose) polymerase‐1 (PARP‐1) and tyrosinase. In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties predictions found that most of the identified compounds exhibited low toxic effects and good absorption and solubility properties.

The study aimed to conduct chemical profiling, acute in‐vivo toxicity evaluation, and the potential anti‐diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan‐induced diabetic rats. The chemical composition was analyzed using GC–MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti‐diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti‐diabetic mechanism. GC–MS analysis displayed the existence of 18 compounds; most of the compounds were fatty acids and their esters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in‐vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD₅₀ value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.

The aim of this study was to investigate the chemical composition and different biological activities of the small twigs (aerial parts before flowering stage) of Maclura spinosa (Willd.) C.C.Berg commonly called “Paper cup flower” family Moraceae. Phytochemical investigation of the of M. spinosa total methanolic extract (MSTME) by different chromatographic and spectroscopic techniques led to the isolation and identification of ten known compounds: arachidic acid methyl ester (1), lupeol acetate (2), glutinol (3), lupeol (4), β-sitosterol and stigmasterol (5), β-sitosterol-3-O-β-D-glucopyranoside (6), apigenin (7), 2,3-dihydrokaempferol (8), orobol (9) and Kaempferol-7-O-β-D-glucopyranoside (10). The gas chromatography-mass spectrometry (GC-MS) analysis of saponifiable and unsaponifiable matters led to the identification of eight and ten compounds, respectively. Moreover, total polyphenolic, total phenolic, and total flavonoid contents were determined by high-performance liquid chromatography (HPLC) analyses of MSTME. In the biological studies, the in-vitro antioxidant activity was determined by the DPPH method, n-but. (MSBF) and EtOAc fractions (MSEF) and MSTME showed the highest activity at 91.5%, 90.8%, and 88%, respectively at concentration 1 mg/mL with comparison to ascorbic acid and quercetin as positive controls. Also, the anti-inflammatory activity was assessed on RAW 264.7 cells, the MSTME (81.50%) and MSEF (48.46%) exhibited the highest activity at a concentration of 10 µg/mL in comparison with standard quercetin. On the other hand, the in-vivo antidiabetic activity was evaluated in streptozotocin (STZ) induced diabetic rats, at a daily oral dose of (300 mg/kg, p.o.) for 15 days, the MSTME and DCM fraction (MSDF) showed a significant reduction in blood glucose levels, total cholesterol and serum triglycerides (p < 0.01). The findings suggest the potential of M. spinosa as a natural product of the development of herbal medicine for the treatment of diabetes and inflammatory diseases.

Croton socotranus Balf.f. shrub is widely used traditionally in Asia as an anti-infective. The study was conducted for metabolite profiling, oral acute toxicity and antioxidant studies, antimicrobial activity and anticancer effect against human hepatoma (HepG2), breast cancer (MCF-7) and rhabdomyosarcoma (RD) cells. Gas chromatography-mass spectrometry analysis revealed the presence of 39 compounds, predominantly comprising fatty acids (57.76%), sesquiterpenes (24.56%) and triterpenes (9.54%). The n-hexane fraction exhibited promising antimicrobial activity and displayed a potent anti-tumour effect against HepG2, MCF-7 and RD cells with IC₅₀ values of 3.4, 6.5 and 7.1 μg/mL, respectively. Histological examination revealed significant morphological changes consistent with the changes observed in the apoptotic mechanism of action. The molecular docking study provided insights into the rational binding modes of the identified compounds with phosphoinositide 3-kinase and poly(ADP-ribose)polymerase-1 enzymes. Our findings suggest the potential of C. socotranus as a valuable source of antimicrobial and anticancer agents.

A new series of piperine-carboximidamide hybrids VIa-k was developed as a new cytotoxic agent targeting EGFR, BRAF, and CDK2. The antiproliferative effect against four cancer cells was investigated against erlotinib. Hybrids VIc, VIf, VIg, VIi, and VIk have the highest antiproliferative activity. Compounds VIc, VIf, VIg, VIi, and VIk inhibited EGFR with IC₅₀ values ranging from 96 to 127 nM. Compounds VIf and VIk had the most potent inhibitory activity as BRAF^V600E (IC₅₀ = 49 and 40 nM, respectively) and were discovered to be potent inhibitors of cancer cell proliferation (GI₅₀ = 44 and 35 nM against four cancer cell lines, respectively). Compound VIk, the most effective derivative as an antiproliferative agent, demonstrated potent anti-CDK2 action with an IC₅₀ value of 12 nM, which is 1.5-fold more potent than the reference dinaciclib. Finally, VIc, VIf, and VIk have a high capacity to inhibit LOX-IMVI cell line survival. Graphical Abstract