The Nephroprotective Activity of Boesenbergia Rotunda Rhizome by Reducing Creatinine, Urea Nitrogen, Glutamic Pyruvic Transaminase, and Malondialdehyde Levels in the Blood and Attenuating the Expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 Genes in the Kidney Cortex of Cisplatin-Induced Sprague-Dawley Rats.

Background: Cisplatin chemotherapy induces nephrotoxicity by producing reactive oxygen species, hence, discovering add-on nephroprotective drugs for patients with cancer is challenging. Boesenbergia rotunda has been reported for its antioxidant properties. Purpose: This study aims to explore the nephroprotective mechanism of the ethanol extract of Boesenbergia rotunda rhizome (EEBR) in cisplatin-induced rats. Methods: The rats were randomly assigned into 6 groups: the normal control (treated with saline); the negative control (cisplatin-induced without any treatment); the positive control (treated with quercetin 50 mg/kg BW); and 3 treatment EEBR (125 mg/kg BW; 250 mg/kg BW; 500 mg/kg BW) groups for 10 days. The % relative organ weight, kidney histopathology, and nephrotoxicity biomarkers expression were evaluated. Results: EEBR decreased creatinine, urea nitrogen, glutamic pyruvate transaminase, and malondialdehyde levels in the blood of cisplatin-induced rats. An insignificant increase in GOT was observed in rats treated with the highest dose of EEBR. EEBR did not significantly alter the BW and the % kidney relative weight. An abnormal shape of the Bowman capsule is observed in the negative control group. EEBR reduced the expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 genes in rats' kidneys. Conclusion: Boesenbergia rotunda could be considered a potential candidate for add-on therapy in cisplatin-treated patients, but further studies are needed to verify its efficacy and safety.

Molecular dynamics study of stigmasterol and beta-sitosterol of Morinda citrifolia L. towards α-amylase and α-glucosidase.

Previous in vivo studies of Morinda citrifolia (Rubiaceae) reported that the extract inhibited α-amylase and reduced blood glucose levels in streptozotocin-induced diabetes mice. Moreover, molecular docking studies confirmed that ursolic acid and sterol compounds contained in the fruit interacted with important residues in the binding site of α-amylase and α-glucosidase. Our work aimed to study the complex stability of stigmasterol (which has been isolated from the M. citrifolia fruit for the first time) and beta-sitosterol towards α-amylase and α-glucosidase by employing molecular dynamics simulation on GROMACS 2016.3 embedded with the AMBER99SB-ILDN force field. The simulation was carried out for 100 ns at 310 oK. Based on the RMSD and RMSF graphs, the complexes of stigmasterol/α-amylase and stigmasterol/α-glucosidase are more stable compared to acarbose, the known inhibitor of both enzymes. Moreover, beta-sitosterol indicates a better stability complex with α-glucosidase compared to that of acarbose. Interestingly, the affinity of stigmasterol and beta-sitosterol to both enzymes, in terms of the total binding energy, is stronger than that of acarbose. Taken together, stigmasterol and beta-sitosterol in M. citrifolia fruit may have the potency to be developed as α-amylase and α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

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 Study of Phytosterols in Lygodium microphyllum Towards SIRT1 and AMPK, the in vitro Brine Shrimp Toxicity Test, and the Phenols and Sterols Levels in the Extract.

Background: Lygodium microphyllum is a fern plant with various pharmacological activities, and phytosterols were reported contained in the n-hexane and ethyl acetate extract of this plant. Phytosterols are known to inhibit steatosis, oxidative stress, and inflammation. Sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are the key proteins that control lipogenesis. However, information about L. microphyllum on SIRT1 and AMPK is still lacking. Purpose: This study aims to investigate the binding mode of phytosterols in L. microphyllum extract towards AMPK and SIRT1, and the toxicity of the extract against brine shrimp (Artemia salina) larvae, and to determine the phenols and sterols levels in the extract. Methods: The molecular docking was performed towards SIRT1 and AMPK using AutoDock v4.2.6, the toxicity of the extract was assayed against brine shrimp (Artemia salina) larvae, and the phytosterols were analyzed by employing a thin layer chromatography densitometry, and the total phenols were by spectrophotometry. Results: The molecular docking study revealed that ß-sitosterol and stigmasterol could occupy the active allosteric-binding site of SIRT1 and AMPK by binding to important residues similar to the protein's activators. The cold extraction of the plant yields 15.86% w/w. Phytochemical screening revealed the presence of phenols, steroids, flavonoids, alkaloids, and saponins. The total phenols are equivalent to 126 mg gallic acid (GAE)/g dry extract, the total sterols are 954.04 µg/g, and the ß-sitosterol level is 283.55 µg/g. The LC50 value of the extract towards A. salina larvae is 203.704 ppm. Conclusion: Lygodium microphyllum extract may have the potential to be further explored for its pharmacology activities, particularly in the discovery of plant-based anti-dyslipidemic drug candidates. However, further studies are needed to confirm their roles in alleviating lipid disorders.

Investigating the Effect of Adherence to Antipsychotic Therapy on the Length of Stay and Number of Hospitalizations in Patients with Schizophrenia - A Descriptive Analysis.

Background: Optimizing long-term outcomes in schizophrenia treatment requires effective pharmacological interventions. Medication adherence is known to influence clinical outcomes, yet there is a scarcity of studies examining its correlation with factors like Length of Stay (LOS) and re-hospitalization frequency. These outcomes are crucial indicators of how medication adherence affects overall patient well-being. Purpose: This study aims to describe the effect of medication adherence on the length of stay (LOS) and number of hospitalizations in patients with schizophrenia. Patients and Methods: A total of 157 subjects from the West Java Psychiatric Hospital were included in this cross-sectional retrospective study. Data, including demographics, comorbidities, duration of illness, antipsychotic adherence, LOS, and the number of hospitalizations, were collected from the patients' medical records. All the data were analyzed using the Chi-Square (χ²) test with a significance level set at p < 0.05. Results: Our findings showed that 88% of all schizophrenia inpatients were in the nonadherence group. The highest (40.7%) LOS (>30 days) was found in the non-adherence group with discontinued therapy/stopped therapy group, while the highest percentage of patients with less than five hospitalizations was identified in the obedient and regular therapy group (94.4%). In the statistical results, we observed a significant association between therapy adherence (p = 0.043) and therapy regimen (p = 0.014) with gender. Additionally, the distinction between male and female schizophrenia patients demonstrated statistical significance (p = 0.000). Conclusion: In this study, therapy adherence and therapy regimen were found to have a significant association with gender, as well as differences between the number of male and female schizophrenia patients that were statistically significant. While other variables may exhibit clinical associations, their statistical significance has not been fully depicted. The results of this study could be preliminary study for subsequent observational studies.

Chitin Extracted from the Shell of Blue Swimming Crabs (Portunus pelagicus Linn.) Inhibits NF-kappaB p65 in Ethanol-Induced Gastric Ulcerative Wistar Rats.

Peptic ulcer disease is generated by the activation of NF-kappaB activity. A recent clinical study reported a significant increase in NF-kappaB2 gene expression in 79 samples of peptic ulcer patients compared to the control group. Moreover, the deacetylated chitin could alter the translocation of NF-kappaB p65 to the nucleus. Considering this, our work aims to explore the effect of chitin extracted from the shell of blue swimming crabs (Portunus pelagicus Linn.) towards NF-kappaB p65 levels in ethanol-induced gastric ulcerative Wistar rats. The shells are found abundantly as the waste of seafood processing in the northern part of West Java, Indonesia. In this study, chitin extraction was carried out using the microwave-assisted extraction method by employing choline chloride (C5H14ClNO) and DL-malic acid (C4H6O5) as the solvents. The inhibitory activity assay of chitin on the expression of NF-kappaB p65 was performed by using Western blot. The extraction yielded a good quality of chitin with a deacetylation degree of 30.8026%, molecular weight of 3.35 × 105 Da, and a negligible heavy metals level. Moreover, chitin extract at doses of 150, 300, and 600 mg/kg BW significantly reduced the percentage of gastric ulcer index compared to the negative control group. Meanwhile, chitin extract at doses of 300 and 600 mg/kg BW significantly inhibited NF-kappaB expression compared to the negative control group. Histopathological examination demonstrated a decrease in the number of necrotic cells and fat degeneration in the gastric mucosa and an increase in normal cells. Taken together, chitin extract obtained from the shells of blue swimming crabs may be able to prevent gastric ulcers induced by ethanol via the inhibition of NF-kappaB p65; however, further studies are needed to verify its anti-ulcerative properties.

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.

Role of the AMPK/SIRT1 pathway in non­alcoholic fatty liver disease (Review).

Non­alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP­activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.

The Evolution of Pharmacological Activities Bouea macrophylla Griffith In Vivo and In Vitro Study: A Review.

Bouea macrophylla Griffith (B. macrophylla) is one of the many herbal plants found in Asia, and its fruit is plum mango. This plant is rich in secondary metabolites, including flavonoids, tannins, polyphenolic compounds, and many others. Due to its bioactive components, plum mango has powerful antioxidants that have therapeutic benefits for many common ailments, including cardiovascular disease, diabetes, and cancer. This review describes the evolution of plum mango's phytochemical properties and pharmacological activities including in vitro and in vivo studies. The pharmacological activities of B. macrophylla Griffith reviewed in this article are antioxidant, anticancer, antihyperglycemic, antimicrobial, and antiphotoaging. Each of these pharmacological activities described and studied the possible cellular and molecular mechanisms of action. Interestingly, plum mango seeds show good pharmacological activity where the seed is the part of the plant that is a waste product. This can be an advantage because of its economic value as a herbal medicine. Overall, the findings described in this review aim to allow this plant to be explored and utilized more widely, especially as a new drug discovery.

The Effects of Antioxidants from Natural Products on Obesity, Dyslipidemia, Diabetes and Their Molecular Signaling Mechanism.

Obesity is a risk factor that leads to the development of other diseases such as dyslipidemia and diabetes. These three metabolic disorders can occur simultaneously, hence, the treatment requires many drugs. Antioxidant compounds have been reported to have activities against obesity, dyslipidemia and diabetes via several mechanisms. This review aims to discuss the antioxidant compounds that have activity against obesity, dyslipidemia and diabetes together with their molecular signaling mechanism. The literature discussed in this review was obtained from the PUBMED database. Based on the collection of literature obtained, antioxidant compounds having activity against the three disorders (obesity, dyslipidemia and diabetes) were identified. The activity is supported by various molecular signaling pathways that are influenced by these antioxidant compounds, further study of which would be useful in predicting drug targets for a more optimal effect. This review provides insights on utilizing one of these antioxidant compounds as opposed to several drugs. It is hoped that in the future, the number of drugs in treating obesity, dyslipidemia and diabetes altogether can be minimized consequently reducing the risk of side effects.

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.

Effect of the roselle (Hibiscus sabdariffa L.) calyces drink on the physiological parameters of healthy adult subjects.

The calyx of roselle (Hibiscus sabdariffa L.) has been the focus of attention of several studies, and although earlier studies on this plant showed it to possess antilipidemic and antidiabetic activities, none of these studies have assessed the effects of this plant on the physiological parameters of healthy subjects. The present study determined the effects of roselle calyx beverages on blood pressure, abdominal circumference, body mass index (BMI), hematological and urinary parameters, and the lipid profile of healthy subjects. Healthy subjects (n=30) were treated with a 200 ml roselle calyx beverage each morning and evening for 30 consecutive days. Every week the subjects were asked to perform some physical activity by following the Young Men's Christian Association step test. This study used a pre-post quasi-experimental design. Blood samples were taken before (day-0) and after the intervention (day-30). There was an increase in the levels of high-density lipoproteins (from 47.0 to 49.5 mg/dl; P=0.015), and a significant decrease in both systolic and diastolic (P=0.036 and P=0.030, respectively), and the abdominal circumference of the subjects (P=0.005). However, total cholesterol levels (191.2 to 191.9 mg/dl; P=0.821) and low-density lipoprotein levels (129.8 to 133.5 mg/dl; P=0.249) were slightly increased, although not significantly. A lower level of triglycerides (114.3 to 107.4 mg/dl; P=0.269) and very-low-density lipoprotein levels (22.8 to 21.4 mg/dl; P=0.681) was observed. No significant differences were detected in the BMI or the urinalysis parameters were identified. Based on these results, roselle (Hibiscus sabdariffa L.) may be used as a supplement to prospectively improve the health status of subjects. No serious adverse effects were observed during this trial.

Potential of Ageratum conyzoides in Inhibiting Nitric Oxide Synthase.

<b>Background and Objective:</b> Inflammation occurs <i>via</i> several mechanisms, one of which includes the production of Nitric Oxide (NO) catalyzed by inducible nitric oxide synthase (iNOS), which is inhibited selectively by isothioureas. <i>Ageratum conyzoides</i> L. has shown activity in reducing pain and inflammation, although the molecular mechanism had not been undertaken. The objectives of this work were (1) to study the mechanism of anti-inflammatory activity of <i>A. conyzoides</i> through inhibition of iNOS, (2) to correlate the iNOS inhibitory activity of the plant with the total flavonoid content of the plants and (3) to identify the flavonol synthase (FLS), an enzyme that catalyzes the production of quercetin. <b>Materials and Methods:</b> The inhibitory activity against iNOS was assayed by <i>in vitro</i> method. The total flavonoids (calculated as quercetin) of <i>A. conyzoides</i> were determined by fluorometry. The protein extraction of the leaves was carried out by employing Laing and Christeller's (2004) method, followed with SDS-PAGE. <b>Results:</b> The inhibitory activity (IC₅₀) of ethanol extract and ethyl acetate fraction of <i>A. conyzoides</i> against iNOS was 92.05 and 4.78 µg mL¹, respectively. Pearson correlation analysis resulted in 0.548 (ethanol extract) and 0.696 (ethyl acetate fraction). The total flavonoids (calculated as quercetin) contained in the ethanol extract and ethyl acetate fraction of <i>A. conyzoides</i> were 0.71 and 7.65%, respectively. The FLS in <i>A. conyzoides</i> leaves was identified at 31 kDa. <b>Conclusion:</b> <i>A. </i>c<i>onyzoides</i> L. is potential in inhibiting iNOS due to quercetin contained in the leaves. This report will add a scientific insight of <i>A. conyzoides</i> for biological sciences.

Sub-chronic toxicity of Garcinia atroviridis Griff Fruit's ethanol extract on Wistar rats (Ratus norvegicus).

Garcinia atroviridis Griff. (GA) is a tropical fruit that commonly used as a traditional medicine to this day. This study was conducted to determine the sub-chronic toxicity effect of GA fruits ethanol extract on body weight, clinical hematology and biochemical parameters, and organ's histopathology. This study is an experimental research by oral treatments for 90 days with completely randomized design. The treatment group consists of five classes. Each class was given the treatment with a dosage of 50 mg/kg BW, 200 mg/kg BW, 800 mg/kg BW and satellite group with 2% PGA, or 800 mg/kgBW. Based on ANOVA and advanced Tukey test results using SPSS, the hematological parameters such as mean corpuscular volume, mean corpuscular hemoglobin concentration, and white blood cell had significant differences with the control group. In the biochemical parameters, the serum glutamic-oxaloacetic transaminase values and triglycerides (in male rats), serum glutamic-pyruvic transaminase and creatinine (in female rats) had significant differences with the control group. In conclusion, GA fruits ethanol extract is safe and non toxic to body weight, clinical hematology and biochemical parameters, and histopathology of ten organs.