Breast cancer (BC) is a multifactorial disease involving many pathways and target molecules. Multi-target therapy through multi-compound herbal medicines is an alternative strategy to treat BC. In the present study, we elucidate the molecular mechanism of Ocimum basilicum (OB) as an anticancer agent using system bioinformatic approach and investigate its cytotoxic effect against MCF-7 cells. We performed network pharmacology (NP) and molecular docking studies to provide scientific information regarding the underlying anti-BC mechanism of OB. Based on topology parameters obtained from protein-protein interaction (PPI), we identified six potential targets that play a significant role in the network including SRC, PI3KCA, EGFR, ESR1, AKT1, and MAPK1. Furthermore, consensus docking suggested rutin, quercetin-3-O-diglucoside, and kaempferol-3-O-β-D-rutinoside as the potential compounds of OB. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the cytotoxic effect of OB might be related to the modulation of several pathways such as PI3K-Akt, VEGF, and HIF-1, breast cancer, and estrogen signaling pathways. The in vitro assay revealed that various extracts of OB demonstrated cytotoxic effects against MCF-7 with IC₅₀ = 231 µg/mL (OB ethanolic extract), 408 µg/mL (OB methanolic extract), 479 µg/mL (OB ethyl acetate extract), 1887 µg/mL (OB n-hexanoic extract) and 767 µg/mL (OB butanolic extract) respectively.

Curcuma xanthorrhiza Roxb, Phyllanthus niruri L., and Morinda citrifolia L. are Indonesian medicinal herbs used empirically as traditional therapeutics for maintaining health. The cocktail extract of these three plants (CECPM) had been developed and demonstrated immunostimulant activity in rats. This study aimed to evaluate the acute and subchronic toxicity of CECPM in vivo. The acute toxicity assay was conducted by orally administering a range dose of CECPM (313, 625, 1250, 2500, or 5000mg/kg body weight (bw) on female mice once and then evaluating the toxic symptom every day for 14days later. The chronic toxicity test was carried out by giving various doses of CECPM (600, 800, and 1000mg/kg·bw) to female and male rats orally continuously for 90 consecutive days. The signs of toxicities were evaluated at the 90- and 28 days postadministration. The acute oral toxicity assays showed that there was no toxic syndrome and mortality found during the period of the experiment. The lethal dose level (LD₅₀) of CECPM was more than 5000g/kg, which was categorized as practically non-toxic. Meanwhile, in the sub-chronic toxicity study, some parameters tested at 90 days postadministration and after 28 days of withdrawal, such as the body weight, relative organ weight, food intake, hematological and biochemical blood parameters, and also histopathological examination of five primary tissues (heart, liver, kidney, spleen, and lung) revealed no abnormalities. There was no-observed adverse effect level (NOAEL) for the present study of CECPM 1000mg/kg·bw of the rat. Therefore, it is concluded that the orally administered CECPM was relatively nontoxic during acute and subchronic toxicology studies.

Bryonia dioicais a member of the Cucurbitaceae that produces bioactive secondary metabolites (PSM), especially steroidal cucurbitacins. Tubers accumulate cucurbitacins, tetrahydrocucurbitacins, bryonioside, and polyphenols such as kaempferol and isovitexin. Through in vitro and simulation studies, this study explores the potential estrogenic and antiestrogenic properties ofBryonia dioica.In silicostudy was performed by molecular docking simulation to predict the binding affinity of BryoniaPSM in Estrogen Receptor Alpha using Molegro Virtual Docker ver 6.0. Thein vitroinvestigation of a methanolic tuber extract used MCF-7 cells, a breast cancer cell line with estrogen receptor (ER), in a medium with or without estradiol. We also analyzed the effect of the extract on the expression of the estrogen-dependentpS2gene using real-time polymerase chain reaction (RT-PCR). Molecular docking showed that Cucurbitacin-E exhibited the best binding affinity to the estrogen receptor with binding sites at His 524, Gly 521, Arg 394, Glu 353, and Leu 391. Methanolic extract ofBryonia dioicaexhibited cytotoxic activity in MCF-7 cells with IC50 = 185 µg/mL (in medium without E2) and IC50 = 125 µg/mL (in medium with E2). In media with and without estrogen, it can stimulate the expression of thepS2gene at a concentration of 50 µg/mL, a marker for estrogenic activity. The results suggest thatBryonia dioicacontains phytoestrogenic PSM with ER agonistic and cytotoxic activities.

Hyperglycaemia is one condition related to inflammation leading to insulin signalling impairment. This study was conducted to investigate the insulin sensitivity improvement of Sambiloto (Andrographis paniculata (Burm. f.)) Nees extract in insulin resistance-induced HepG2 (IR-HepG2) cells by stimulating insulin sensitivities and inhibiting inflammatory response. Sambiloto extract at 2 µg/mL revealed glucose uptake stimulation and up-regulating GLUT-2 and IRS-1 gene expression, and inhibited pro-inflammatory cytokine IL-6 gene expression in IR-HepG2 cells. Phytochemical analysis showed that the total phenolic level and andrografolide content of Sambiloto extract were 2.91 ± 0.04% and 1.95%, respectively. This result indicated that Sambiloto extract ameliorated insulin resistance in high glucose-induced IR-HepG2 cells via modulating the IRS-1/GLUT-2 pathway due to IL-6 inhibition. These findings suggested that Sambiloto extract had potency as an anti-inflammatory and insulin-resistance improvement in IR-HepG2 cells.

This study aimed to evaluate the anti-inflammatory activity of the combination of Ardisia humilis Vahl. and Curcuma xanthorrhiza Roxb. (AC) extract in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. AC was administered orally to OA rats (240, 480, and 960 mg/kg bw) for three weeks. The control and model groups comprised OA rats treated with diclofenac sodium and carrier, respectively. AC-treated rats exhibited a significant reduction in oedema volume compared to those of the model group (p < 0.05). Notably, AC, at 960 mg/kg bw, significantly decreased inflammatory cytokines TNF-α and IL-1β, along with matrix metalloproteinase-9 (MMP-9) levels compared to those of the model group (p < 0.05). AC's attenuation of OA progression was also observed through haematoxylin and eosin (H&E) and Safranin O-fast green analysis. A phytochemical study showed AC contained phenolic, flavonoid, curcumin, demethoxycurcumin, and bisdemethoxycurcumin compounds. This study concludes that AC alleviated OA progression through anti-inflammatory effects and depressed MMP-9 levels.