Erythrina subumbrans (Hassk) Merr. (Fabaceae) Inhibits Insulin Resistance in the Adipose Tissue of High Fructose-Induced Wistar Rats.

Background: The twigs and roots of Erythrina subumbrans (Hassk). Merr. Was reported to possess antidiabetic activity by reducing the activity of α-glucosidase and α-amylase. TNF-α is a pro-inflammatory cytokine in obesity and diabetes mellitus (DM). It inhibits the action of insulin, causing insulin resistance. Adiponectin is an anti-inflammatory peptide synthesized in white adipose tissue (WAT) and its high levels are linked with a decreased risk of DM. However, information about the effect of Erythrina subumbrans (Hassk). Merr. on insulin resistance are still lacking. Purpose: To obtain the effects of the ethanol extract of E. subumbrans (Hassk) Merr. leaves (EES) in improving insulin resistance conditions. Methods: The leaves were collected at Ciamis, West Java, Indonesia, and were extracted using ethanol 96%. The effects of EES were studied in fructose-induced adult male Wistar rats by performing the insulin tolerance test (ITT) and assessing blood glucose, TNF-α, adiponectin, and FFA levels. The number of WAT and BAT of the adipose tissues was also studied. The total phenols and flavonoids in EES were determined by the spectrophotometric method and the presence of quercetin in EES was analyzed using the LC-MS method. Results: EES significantly reduced % weight gain, TNF-α levels, and increased adiponectin levels in fructose-induced Wistar rats. EES significantly reduced the FFA levels of fructose-induced Wistar rats and significantly affected the formation of BAT similar to that of metformin. All rats in EES and metformin groups improved insulin resistance as proven by higher ITT values (3.01 ± 0.91 for EES 100 mg/kg BW; 3.01 ± 1.22 for EES 200 mg/kg BW; 5.86 ± 3.13 for EES 400 mg/kg BW; and 6.44 ± 2.58 for metformin) compared with the fructose-induced group without treatment (ITT = 2.62 ± 1.38). EES contains polyphenol compounds (2.7638 ± 0.0430 mg GAE/g extract), flavonoids (1.9626 ± 0.0152 mg QE/g extract), and quercetin 0.246 µg/mL at m/z 301.4744. Conclusion: Erythrina subumbrans (Hassk). Merr. extract may have the potential to be further explored for its activity in improving insulin resistance conditions. However, further studies are needed to confirm its role in alleviating metabolic disorders.

Botanical and pharmacognostic investigation of Strobilanthes kalimantanensis.

Under a hidden waterfall in the interior of the tropical rainforest of East Kalimantan, a new medicinal plant that produces essential oil (EO) was found with the name Strobilanthes kalimantanensis. The aim was to investigate the botanical and evaluate the pharmacognostic characteristics of S. kalimantanensis leaves from East Kalimantan, Indonesia. Pharmacognostic studies can provide recommendations for establishing quality control standards or guidelines for cultivating, harvesting, and processing S. kalimantanensi s to ensure the consistent and reliable quality of medicinal products. Characteristic methods of S. kalimantanensis leaves include botanical macroscopic, fluorescence, physicochemical, and phytochemical evaluation. The plant characteristics of this plant are similar to S. kunthia and S. reptans but can be differentiated in the leaves and flowers. Fluorescence assay with sodium hydroxide 5% shows unique characteristics of secondary metabolites based on their ability to form dark green with black precipitate in Ultraviolet 365 nm. The physicochemical characteristics showed yield, water content, water-soluble, ethanol soluble, total ash value, and acid-insoluble ash. Phytochemicals showed the presence of alkaloids, polyphenols, terpenoids, and EO containing 23% trans-anethole. This evaluation report details the chemical composition, identity, and safety of S. kalimantanensis leaves.

Safety Assessment of Schleichera oleosa Lour. Leaves Extract: Acute and Subchronic Studies.

<b>Background and Objective:</b> <i>Schleichera oleosa</i> (Sapindaceae) has been reported to be useful in traditional medicine and it has some potential pharmacological activities, such as anticancer, antioxidant and antimicrobial activities. This study aimed to assess its safety to provide complete data required for the development of <i>S. oleosa</i> as herbal medicine. <b>Materials and Methods:</b> The safety assessment of the extract was carried out by testing acute and subchronic toxicity in mice (male and female) and rats (male and female), respectively. The doses used in the acute toxicity test were 1000, 2000, 3000, 4000 and 5000 mg kg¹ of body weight and those in the subchronic treatment were 100, 200 and 400 mg kg¹ of body weight. <b>Results:</b> In the acute toxicity test, the <i>S. oleosa</i> leaf extract at all doses indicated that the LD₅₀ value of the extract was higher than 5000 mg kg¹ b.wt., which suggested that this extract is practically non-toxic according to the toxicity criteria. Furthermore, the subchronic toxicity test found that the administration of the extract to male and female rats at a daily dose of 100 and 200 mg kg¹ b.wt., for 90 days did not cause any significant change in blood haematology, blood biochemistry and histopathological picture of liver, kidney, heart, lymph and lung. Despite there being a significant increase in white blood counts, long-term use of the <i>S. oleosa</i> leaf extract is relatively safe. <b>Conclusion:</b> The results provided evidence regarding the potential of <i>S. oleosa</i> leaves to be used as herbal medicine. However, further research needs to be done to verify that activity and its safety in long-term use.

Review of the Case Reports on Metformin, Sulfonylurea, and Thiazolidinedione Therapies in Type 2 Diabetes Mellitus Patients.

Type 2 diabetes mellitus (T2DM) is the world's most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic ß-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic ß-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of ß-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords 'metformin OR sulfonylureas OR thiazolidinediones AND case reports', filtered to 'free full text', 'case reports', and '10 years publication date'. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects.

Pharmacology activity, toxicity, and clinical trials of Erythrina genus plants (Fabaceae): an evidence-based review.

The concept of using plants to alleviate diseases is always challenging. In West Java, Indonesia, a local plant, named dadap serep has been traditionally used to reduce blood glucose, fever, and edema, by pounding the leaves and applying them on the inflamed skin, or boiled and consumed as herbal tea. This plant belongs to the Erythrina genus, which covers approximately 120 species. The scope of this review (1943-2023) is related to the Global Development Goals, in particular Goal 3: Good Health and Wellbeing, by focusing on the pharmacology activity, toxicity, and clinical trials of Erythrina genus plants and their metabolites, e.g., pterocarpans, alkaloids, and flavonoids. Articles were searched on PubMed and ScienceDirect databases, using "Erythrina" AND "pharmacology activity" keywords, and only original articles written in English and open access were included. In vitro and in vivo studies reveal promising results, particularly for antibacterial and anticancer activities. The toxicity and clinical studies of Erythrina genus plants are limitedly reported. Considering that extensive caution should be taken when prescribing botanical drugs for patients parallelly taking a narrow therapeutic window drug, it is confirmed that no interactions of the Erythrina genus were recorded, indicating the safety of the studied plants. We, therefore, concluded that Erythrina genus plants are promising to be further explored for their effects in various signaling pathways as future plant-based drug candidates.

Molecular docking and molecular dynamics studies of bioactive compounds contained in noni fruit (Morinda citrifolia L.) against human pancreatic α-amylase.

Human pancreatic α-amylase inhibition is currently a promising therapeutic target against type 2 diabetes (DMT2) because it can reduce aggressive digestion of carbohydrates into absorbable monosaccharides. In Indonesia, medicinal plants, e.g. Morinda citrifolia fruit, have been empirically utilized as a blood-sugar reducer, however, the inhibitory activity of compounds in this plant against human pancreatic α-amylase is still limited or none. Therefore, this study aimed to test the interaction of 7 compounds (americanin, asperulosidic acid, damnacanthal, quercetin, rutin, scopoletin, and ursolic acid) contained in noni fruit against human pancreatic α-amylase by molecular docking and molecular dynamics and compared their binding modes with that of acarbose. Results of the molecular docking simulation indicated that the ursolic acid compound possesses the best binding energy (-8.58 kcal/mol) and comparable to that of acarbose (-8.59 kcal/mol). The molecular dynamics study at 100 ns simulation, the values of RMSD, RMSF, the radius of gyration (Rg), the solvent-accessible surface area (SASA), principal component analysis (PCA), and MM-PBSA binding free energy were stable and identical to those of acarbose. It could be concluded that ursolic acid might be potential in inhibiting human pancreatic α-amylase, thus, potential to be developed as an anti-DMT2 drug candidate. Communicated by Ramaswamy H. Sarma.

Phytosome drug delivery system for natural cosmeceutical compounds: Whitening agent and skin antioxidant agent.

Plants have been used as traditional medicine since ancient times for treating the diseases, metabolite active compounds from plants have excellent bioactivity, and pharmacological properties from plants are used as skin whitening agent and antioxidant in multiple mechanisms of action. However, these compounds have physicochemical limitations in terms of its poor solubility and penetration into the cells membrane. Phytosome drug delivery system can be the primary choice to improve the physicochemical properties, which allows increasing the effectiveness. This review aimed to summarize and discuss the phytosome formulations of potential active compounds as skin whitening agent and skin antioxidant, which obtained from Scopus, PubMed, and Google Scholar databases. We assessed that the main purpose of these phytosome formulations was to improve penetration, stability, and solubility of the active compounds. These studies proved that phytosome formulations can improve the physicochemical characteristics and effectiveness of compounds. The phytosome drug delivery system becomes a promising modification technique for natural compounds due to the ability to improve the physicochemical properties and increase the effectiveness. Phytosome formulation could be the excellent approach for cosmeceutical product with good effectivity in the future.

Antibacterial activity and subchronic toxicity of Cassia fistula L. barks in rats.

Increasing incidence of antibiotic resistance necessitates the development of more potent antibiotics. The aim of this work was to evaluate the antibacterial activity of Cassia fistula L. barks as an alternative agent for resistant pathogenic bacteria. The C. fistula barks were extracted with ethanol, followed by partition of the extract to give n-hexane, ethyl acetate and water fractions. An in vitro antibacterial assay was conducted to evaluate inhibitory activity of the extract and fractions against Salmonella typhosa and Shigella dysenteriae. An in vivo antibacterial activity was examined using S. typhosa-infected mouse models, in which the colony number of S. typhosa were counted from the infected rats' feces. Assesment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occured in biochemical parameters and hystopatological conditions of livers and kidneys. The results showed that the ethanol extract inhibited the growth of both S. typhosa and S. dysenteriae with the MIC of 0.3125% w/v, and the ethyl acetate fraction with the MIC of 0.625% b/v. In the in vivo antibacterial assay, the extract at three doses decreased the colony number of S. typhosa significantly, and after the fourth to sixth days, the precentage of decrease reached more than 90% by 1000 mg/kg dose. The subchronic toxicity test revealed that after the extract exposured for 90 days, a dose of 1000 mg/kg induced liver and kidney damages histologically, however, it returned to normal condition after 30 days of recovery. The results of this study indicated that the extract of C. fistula L. barks had potent in vivo antibacterial activity against S. typhosa as sample of resistant bacteria, and is safe to be used as a herbal medicine, preferably at a dose lower than 1000 mg/kg.

Kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii Korth. inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway.

Plants consumed by non-human primates represent potential drug sources for human disease management. In this study, we isolated kaempferol-3-O-rhamnoside as an active compound from the leaves of Schima wallichii Korth., a plant commonly consumed by non-human primates. Its anti-cancer activities, including its ability to induce apoptotic mechanisms, were investigated in MCF-7 breast cancer cells. Results showed that in MCF-7 cells, kaempferol-3-O-rhamnoside inhibits cell proliferation in a dose-dependent manner and promotes apoptosis via the activation of the caspase signaling cascade, which includes caspase-9, caspase-3 and PARP. Our results provide a basis for further exploration of kaempferol-3-O-rhamnoside as an active compound for potential anti-cancer therapeutics.