Acute pancreatitis develops as a local inflammatory condition of the pancreas due to a wide range of factors including overdose of alcohol or drugs, gall stones, etc. At present, medications based on herbal formulations have gained importance due to their better safety profile. Current study assessed the pharmacological effects of Pancogrit, an herbal medicine, in caerulein and TNF-α-induced in vitro pancreatitis models. A comprehensive evaluation of phytometabolites present in Pancogrit was conducted and 85 phytometabolites were identified through UPLC-QTOF-MS and UPLC-UV. The bioactivity and mode of action of Pancogrit were assessed in caerulein-induced AR42J (rat pancreatic acinar) cells, TNF-α-induced PANC-1 (human pancreatic duct) cells, and NF-κB reporter cells. Pancogrit was found to decrease the elevated amylase and lipase activity in caerulein-induced AR42J cells. It ameliorated the increased ROS levels, IL-6, IL-8 release and NF-κB activity in TNF-α-induced PANC-1 and NF-κB reporter cells. Pancogrit also downregulated IL-6, IL-1β, ICAM-1, and STAT3 gene expression in PANC-1 cells. Moreover, Pancogrit inhibited the protein expression levels of phosphorylated STAT3, phosphorylated and total JAK2 in TNF-α-induced PANC-1 cells. Taken together, Pancogrit is a clinically relevant therapeutic agent for mitigation of pancreatitis.

Hops (Humulus lupulus) was used to treat menopausal symptoms because it contains phytoestrogens. Since these compounds prevent cardiac ischemic diseases, it was evaluated whether oral administration of an ethanol extract (Hops-T) to rats during a week could reduce cardiac post-ischemic dysfunction. Moreover, its effects on visceral peristaltism and the mechanisms of action were studied. Rat isolated hearts were perfused inside a calorimeter, left intraventricular pressure and calorimetrical signals were recorded during ischemia/reperfusion. The NO-synthases and mKATP channels roles were evaluated by respectively blocking them with L-NAME and 5-HD before ischemia. After the experiment, western-blots for cellular pathways (p-AKT, p-PKCϵ, GSK3b and BCL-2) were done. In isolated intestinal, bladder and uterine rat tissues, contractile carbachol concentration-response curves (CCh-CRCs) were performed. The HPLC-DAD mainly showed prenylated flavonoids, beta acids and isoflavones. Hops-T increased contractile and energetic recoveries more significantly in the male rat hearts compared to females, due to beneficial NO production and mitochondrial mKATP channels activation. However, the p-AKT, p-PKCϵ, GSK3b or BCL-2 expressions were not affected after reperfusion. Hops-T inhibited CCh-CRCs in intestinal, bladder and uterine tissues through a non-competitive mechanism. Additionally, it showed a non-competitive antagonism of the Ca2+-CRCs in bladder tissues, similar to the effects observed with verapamil. In conclusion, oral Hops-T prevented cardiac mitochondrial and contractile ischemic dysfunction, and it was a good visceral antispasmodic medicine by interfering with Ca2+ influx. This is a significant finding since it pre-clinically supports the use of hops extract for prevention of visceral spasms and cardiac diseases associated with coronary insufficiency.

Curcumin is well known for its diverse health benefits based on the traditional and current scientific evidence. The aim of the present study was to evaluate the safety of Maxicuma® made by using proprietary LIMAN technology that involves encapsulation of 40% curcuminoids with lipid matrix. The safety profile was studied with single dose and repeated dose oral administration of Maxicuma® in both rodents and non-rodents. The toxicity study was conducted at a range of 0.5 to 10 gm curcumin equivalent to human dose per day. None of the tested doses in any of the species produced treatment related clinical signs of toxicity with respect to haematology and blood chemistry parameters and mortality. Moreover gross and histopathological findings did not show any remarkable and treatment related changes. The treated animals exhibited normal weight gain and comparable feed intake. Based on the obtained results Maxicuma® up to 220 mg/kg oral dose could be considered as safe, tolerated and no observed adverse effect level (NOAEL) dose in rabbits.

Endophytic fungi from Aglaia argentea have indicated the prospective to produce secondary metabolites with unique activities, making them promising candidates for anticancer drug development. This study aimed to investigate the secondary metabolites produced by Lasiodiplodia theobromae BPPCA144, isolated from A. argentea. L. theobromae BPPCA144 was found to produce seven compounds: 2-phenylethanol (1), tyrosol (2), 2-(4-hydroxyphenyl)acetic acid (3), (-)-mellein (4), colletopeptide B (5), botryorhodine A (6), and (4R*,6R*)-4-hydroxy-6-n-propyl-1-oxacyclohexan-2-one (7). These compounds were isolated using vacuum liquid and radial chromatography, and their chemical structures were elucidated through 1D-NMR, 2D-NMR analysis, compared with previously reported spectral data. Notably, compounds (5) and (7) were identified as original from L. theobromae. Among the tested compounds, compound (2) exhibited the strongest activity against MCF-7 breast cancer cells. However, compounds (1, 3, 5 and 7) showed insufficient activity against CV-1 cell lines (normal kidney fibroblast cells).

Brazil, a vital pineapple producer, faces phytosanitary challenges, mainly due to fusariosis caused by Fusarium guttiforme, which can lead to significant harvest losses. The frequent use of chemical fungicides has disadvantages because they are environmental contaminants. One option to avoid using these compounds is essential oils, which are of natural origin, biodegradable and have notable activity in controlling numerous pathogens. Thus, the present research aimed to evaluate in vitro the potential of citronella essential oil to control the fungus F. guttiforme. The chemical identification of the essential oil components was conducted using gas chromatography with flame ionization detectors and mass spectrometry. The main compounds identified in citronella essential oil were citronellal (35.70%), geraniol (24.63%) and citronellol (15.98%). It was clear that the concentration of 1.050 μL mL−1 of citronella essential oil promoted 100% inhibition of mycelial growth, with no statistically significant difference when compared to the positive control (Tecto® SC). These results confirm citronella essential oil’s remarkable in vitro potential in controlling the fungus F. guttiforme.

Limited treatment options and emerging resistance necessitate the exploration of novel lung cancer therapeutics. This study investigates the potential of Dandang Gendis (Clinacanthus nutans) leaf extract, a Southeast Asian plant, using a combined in vitro and in silico approach. The in vitro study assessed the extract’s cytotoxicity towards A549 lung cancer and TIG-1 fibroblast cells using the WST-1 assay. The in silico analysis identified active compounds, predicted a target protein, performed functional annotation and explored mechanisms through molecular docking and dynamics simulations. The in vitro analysis revealed a significantly higher flavonoid content (177.63 mg QE/g) compared to phenols (45.66 mg GAE/g), suggesting a potential role for flavonoids. Importantly, the extract displayed remarkable selectivity in its cytotoxic effects. It significantly reduced A549 lung cancer cell viability while maintaining high viability in normal TIG-1 fibroblasts, particularly at the 24-hour exposure. While concentrations above 200 μg/ mL significantly decreased the viability of A549 cancer cells, normal TIG-1 fibroblast cells maintained high viability (>50%) at these concentrations. In silico analysis identified isomollupentin 7-O-β-glucoside, isoorientin, and isovitexin, all C-glycosyl flavones, as potential active compounds. These compounds were predicted to act as PD-L1 inhibitors, potentially enhancing T cell-mediated antitumor activity. This aligns with the observed selective cytotoxicity. Overall, this study provides evidence for the potential of the C. nutans extract and its C-glycosyl flavone constituents, particularly the identified compounds, as novel lung cancer therapeutics targeting the PD-L1 pathway for T cell-mediated tumor suppression.

Breast cancer, the most prevalent cancer in women globally, is characterized by a low survival rate. Euphorbia hirta is predicted to exhibit promising antibreast cancer properties. This study aimed to explore the active compounds present in the ethanol extract of E. hirta and elucidate their mechanism for countering breast cancer using computational and experimental methodologies. The active components of the E. hirta ethanol extract were determined using Liquid chromatography high-resolution mass spectrometry. Furthermore, the identified active compounds were subjected to computational analysis involving drug-likeness screening, membrane permeability, bioactivity, toxicity assessment and protein target prediction using QSAR principles followed by molecular docking and molecular dynamics simulations. In vitro experimental investigations included toxicity, rhodamine, apoptosis, cell migration and colony formation assays. These findings indicated that six compounds with drug-like properties and physicochemical features exhibited bioactivity relevant to breast cancer. These compounds, namely, quercetin, luteolin, gallic acid, gentisic acid, quinic acid and caffeic acid, target proteins associated with breast cancer progression, including EGFR, KDR, SRC, FASN, CDK4 and ERBB2. According to molecular docking and dynamics studies, these active compounds bind securely, potentially inhibiting their target protein activity. The ethanol extract of E. hirta was toxic and selective for T47D cells. The extract induced apoptosis and loss of mitochondrial membrane potential in T47D cells, restraining their migration and colony formation. The research findings demonstrate that the extract of E. hirta effectively antagonizes breast cancer by inducing apoptosis, suppressing cellular migration, and inhibiting cell colony formation through the targeted modulation of associated proteins.

Ixoroside, an iridoid glycoside, was isolated from two endemic plants, Nepeta aristata and Nepeta baytopii and its structure was elucidated by comprehensive analysis with NMR and mass spectrophotometers. It was observed that the compound exhibited strong antioxidant activity in phosphomolybdenum-reducing power (55.65±0.02 μg/mL), H2O2 (2.97±0.50 μg/mL), and superoxide anion scavenging (11.31±0.19 μg/mL) activities. It has also been noted that the ixoroside molecule has enzyme inhibitor (7.01±0.001 μg/mL for urease, 19.06±0.51 μg/mL for AChE, 9.90±0.5 μg/mL for BChE, 16.87±0.08 μg/mL for α-amylase, 4.11±0.36 μg/mL for α-glucosidase and 2.23±0.001 μg/mL for tyrosinase) and DNA protective effect (55.14% for Form I) and antibacterial (10 mm against K. pneumoniae, 9.00 mm against E. faecalis and 11.00 mm against S. aureus, 128 μg/mL against E. coli and E. faecalis). In silico studies, density functional theory (DFT) and molecular docking were performed to elucidate ixoroside interaction with enzymes. In enzyme inhibition kinetics, ixoroside exhibited strong interaction with urease (Ki, 0.11 mM, mixed-uncompetitive), α-glucosidase (Ki, 0.10 mM, noncompetitive) and tyrosinase (Ki, 0.10 mM, noncompetitive). Additionally, BChE was observed to interact strongly with α-glucosidase and tyrosinase with binding constants of 0.49, 1.19 and 3.15 μM in molecular docking. Moreover, the pharmacological properties of ixoroside examined by adsorption, distribution, metabolism, excretion and toxicity (ADMET) showed that the molecule has drug-like properties.

Diabetes mellitus (DM) ranks as the fourth cause of death among non-communicable diseases worldwide. Mortalities due to diabetes are associated with high cost, undesirable side effects, and less effectiveness of antidiabetic agents currently in clinical use. Therefore, this study investigated the antidiabetic and antihyperlipidemic potential of two flavonoids, 5,6,7,8-tetramethoxyflavone (1) and 5,6,7,4’-tetramethoxyflavone (2) in streptozotocin-nicotinamide induced diabetic Wistar rats. Oral acute toxicity test was conducted in male Wistar rats using the up and down method by following OECD Guideline 423. The doses, 5 and 50 mg/kg b.w were used for each flavonoid. No clinical signs of toxicity were observed for compound 1 at tested doses while compound 2 resulted in itching, reduced weight, and increased levels of creatinine. The LD50 values were established to be ≥ 50 mg/kg b.w for both compounds. In the evaluation of antidiabetic and antihyperlipidemic efficacy, diabetic Wistar rats were administered with 2.5, 5.0 and 7.5 mg/kg b.w for each compound. Compound 1 lowered the level of fasting blood glucose (FBG) significantly (p < 0.05) while compound 2 lowered FBG with no significant difference (p > 0.05) compared to the negative control. Both compounds did not avert weight loss but reduced the rate of weight loss in a dose-dependent manner. The levels of HDL-C increased with no significant difference (p > 0.05), while the levels of TC, TG, and LDL-C were reduced significantly (p < 0.05) for compound 1 compared to the negative control. Compound 2 reduced the levels of LDL-C, and increased the levels of TG significantly (p < 0.05) compared to the negative control. However, compound 2 resulted in inflation of the urinary bladder, and swelling of stomach, intestines, and testes of diabetic rats. Therefore, this study identifies and recommends 5,6,7,8-tetramethoxyflavone (1) as a promising antidiabetic and antihyperlipidemic agent.

Cancer is a global concern and the potential targeting of cancer stem cells (CSCs) has gained major attention in anticancer drug discovery research. Various natural compounds have shown promising effects in suppressing cancer, prompting scientific interest. In this study, we investigated the anti-CSC properties of schisandracaurin C, a novel compound derived from the Vietnamese plant Schisandra cauliflora. To evaluate its anti-CSC efficacy, we employed the MTT assay, flow cytometry analysis, the caspase-3 assay and a three-dimensional cell culture method, focusing on the teratocarcinoma NTERA-2 cells. Our findings revealed that schisandracaurin C inhibited the growth of NTERA-2 cells with an IC50 value of 16.61±0.13 μM, which was significantly lower than that on HEK-293A healthy embryonic kidney cells (22.72±0.02 μM) (P<0.05). Schisandracaurin C was toxic to NTERA-2 cells within three-dimensional tumorspheres (IC50: 33.47±1.45 μM). The anti-CSC effects of schisandracaurin C on NTERA-2 cells were mediated through apoptosis, as evidenced by increased caspase-3 activity. Schisandracaurin C induced cell cycle arrest at the S phase in NTERA-2 cells. These findings highlight the potential of schisandracaurin C as a promising anti-CSC compound, which warrants further mechanistic and clinical investigations.