Review of the pharmacological properties of marine macroalgae used in the treatment of diabetes mellitus in Indonesia.

Indonesia is the largest archipelagic country in the world, with 70% of its territory covered by oceans that are rich in various types of biological resources. Indonesia's biodiversity has made it possible to develop natural medicine. Marine algae have enormous potential, but the types of marine algae used still need to be more varied. Research on the pharmacology of marine macroalgae has been conducted in Indonesia, but studies on such topic related to diabetes mellitus (DM) still need to be completed. This study provides a comprehensive dataset of pharmacological anti-diabetic potential of marine macroalgae used for managing DM and reports on preclinical trials that provide pharmacological evidence. Data on the Indonesian marine macroalgae used to lower blood glucose were obtained from online sources. The bioactive chemicals of marine macroalgae have been found efficient at blocking several diabetes enzymes in in-vivo and in-vitro studies, and such chemicals have anti-inflammatory, anti-obesity, antioxidant, and other therapeutic benefits. The Google Scholar was used to search for the pharmacological literature with the keywords marine AND macroalgae AND diabetes AND Indonesia. Pharmacological research on the anti-diabetic activity of marine macroalgae has been carried out on five major Indonesian islands, including Sumatra, Kalimantan, Java, Sulawesi, and Papua, which encompassed 12 provinces: Southwest Papua, South Sulawesi, West Kalimantan, Riau Archipelago, Banten, West Java, North Sulawesi, East Java, Yogyakarta, Maluku, Jakarta, and Bengkulu. Articles on preclinical tests (in vitro and in vivo) were also used for the phytochemical problem section. The results briefly describe which class of algae has been widely used in Indonesia as an anti-diabetic. The findings of this research can be utilized to help find DM treatment drugs based on natural resources from marine macroalgae.

Flavonoid from Moringa oleifera leaves revisited: A review article on in vitro, in vivo, and in silico studies of antidiabetic insulin-resistant activity.

Diabetes mellitus (DM) occurs when the body experiences insulin deficiency or is unable to use insulin appropriately, which increases the blood glucose levels over the threshold. Moringa oleifera leaf is a widely used and scientifically proven herbal medicine to treat DM. The demand for the development of new drugs has prompted in vitro, in vivo, and in silico studies of antidiabetic insulin-resistant activity. This study aims to conduct a comprehensive study of the types of flavonoid and nonflavonoid compounds that have antidiabetic activity in insulin resistance mellitus using in vitro, in vivo, and in silico approaches. The literature review was conducted in accordance with the offered reporting items for systematic review. Major bibliographic databases, i.e. Scopus, PubMed, and DOAJ, covering original articles about the aforementioned issues between January 1, 2011 and December 31, 2021 were used. In this study, 274 articles were retrieved, of which 4 were duplicates, and after the titles were read, only 108 were left for analysis. After the abstract screening, 32 articles were eligible for the literature review. The results exhibit that flavonoids, including quercetin and kaempferol, and nonflavonoids, including anthraquinone, cytogluside (glycoside), hemlock tannin, phenolic steroid, and 2-phenylchromenylium (anthocyanins), have potential insulin-resistant antidiabetic activity in vitro, in vivo, and in silico. This has broadened the research into the development of new drugs.

Application of Response Surface Methodology (RSM) for the Optimization of Ultrasound-Assisted Extraction (UAE) of Moringa oleifera: Extraction Yield, Content of Bioactive Compounds, and Biological Effects In Vitro.

This study optimized ultrasound-assisted extraction conditions to maximize the extraction yield, total flavonoid content (TFC), total phenolic content (TPC), and DPP IV enzyme inhibitory activity from Moringa oleifera. The four UAE factors, solvent ratio (A), solvent-solid ratio (B), extraction temperature (C), and extraction time (D), were optimized using response surface methodology (RSM). A Box-Behnken design was used for the experimental design. The optimal conditions were found to be a 50% v/v solvent ratio, a 30% v/w solvent-solid ratio, 35 °C extraction temperature, and 45 min extraction time. The experimental value of extraction yield (R1), TFC (R2), TPC (R3), and DPP IV enzyme inhibitory activity (R4) (87.99% w/w, 56.63 mg QE/g extract, 97.26 mg GAE/g extract, and 93.32% inhibition, respectively) agreed with those predicted by RSM models (88.10% w/w, 56.61 mg QE/g extract, 97.16 mg GAE/g extract, and93.38% inhibition, respectively), thus demonstrating the appropriateness of the model used and the ability of the RSM to optimize the extraction conditions. Excellent DPP IV enzyme inhibitory activity was exhibited by M. oleifera compared with the standard, sitagliptin. While the modeled equation fits the data, the t-test is not significant, suggesting that the experimental values agree with those predicted by the RSM-BBD.

Prevention of Inflammation-Driven Colon Carcinogenesis in Human MUC1 Transgenic Mice by Vaccination with MUC1 DNA and Dendritic Cells.

The preventive efficacy of MUC1-specific DNA immunization on inflammation-driven colon carcinogenesis in human MUC1 transgenic (MUC1.Tg) mice was investigated. Mice were vaccinated with MUC1 DNA mixed with autologous bone-marrow-derived dendritic cells (BMDCs), and then colonic tumors were induced by azoxymethane (AOM) injection and oral administration of dextran sulfate sodium (DSS). Two types of tumors, squamous metaplasia and tubular adenoma, were observed. Both expressed high levels of MUC1 as indicated by the binding of anti-MUC1 antibodies with different specificities, whereas MUC1 expression was not detected in normal colonic mucosa. When mice were immunized with MUC1 DNA + BMDCs, tumor incidence, tumor number, and tumor size were significantly reduced. In contrast, vaccination with MUC1 DNA alone or BMDCs alone was ineffective in reducing tumor burden. Inflammation caused by DSS was not suppressed by the MUC1 DNA + BMDCs vaccination. Furthermore, MUC1 protein expression levels, as judged by anti-MUC1 antibody binding in tumors grown after vaccination, did not significantly differ from the control. In conclusion, an inflammation-driven carcinogenesis model was established in MUC1.Tg mice, closely resembling human colon carcinogenesis. In this model, vaccination with MUC1 DNA + BMDCs was effective in overriding MUC1 tolerance and reducing the tumor burden by a mechanism not affecting the level of colonic inflammation.

Quantification of Enhydrin and Uvedalin in the Ethanolic Extract of Smallanthus sonchifolius Leaves Validated by the HPLC Method.

Yacon leaf (Smallanthus sonchifolius, Asteraceae) ethanolic extracts are widely used in herbal medicine preparation for diabetes. They contain two sesquiterpene lactones (enhydrin (1) and uvedalin (2)) as major bioactive compounds. To provide a suitable method of analysis for the extract's quality control, we developed and validated a simultaneous HPLC-UV method using the compounds as markers. Compounds 1 and 2 were isolated using a freeze crystallization technique followed by a preparative HPLC. Spectrometry data for 1 and 2 were determined and compared to the literature. Chromatographic separation was carried out for 30 min with a mobile phase that used 60% water and 40% acetonitrile and a C18 column (250 × 4.6 mm, 5 µm) as the stationary phase. The flow was set to 1 mL min-1 and detection was conducted at 210 nm. The validation method was conducted according to the ICH guidelines, which included linearity, precision, accuracy, LOD, and LOQ. The calibration curve of both compounds was linear (R 2 > 0.9999), with the limit of detection and quantification as follows, respectively, 0.52 and 1.57 µg/mL for 1, and 0.144 and 0.436 µg/mL for 2. The percentages of recovery and repeatability (%RSD) were, 101.46 and 0.30% for 1, and 97.68 and 0.08% for 2, respectively. The 1 and 2 were 1.67 and 0.88% in the Ykal extract, and 1.26 and 0.56% in the Ycin extract, respectively. The method was found to be linear, precise, accurate, and suitable to be applied for control quality analyses of yacon leaf extract.

Acute and Subchronic Oral Toxicity Evaluation of Herbal Formulation: Piper crocatum Ruiz and Pav., Typhonium flagelliforme (Lodd.) Blume, and Phyllanthus niruri L. in Sprague-Dawley Rats.

Background: The product combination of Piper crocatum Ruiz. and Pav., Phyllanthus niruri Linn., and Typhonium flagelliforme (Lodd.) BL ethanolic extract (SKM) exerts immunomodulatory activity. However, the toxicity profile of the combination has never been investigated. Objective: This study aimed to establish the acute toxicity profile of the SKM product on Sprague-Dawley (SD) rats and its subchronic toxicity profile on female SD rats. Method: The acute and subchronic toxicity tests were conducted in accordance with OECD 423 and OECD 408, respectively. Result: The SKM product was safe up to 5000 mg/kg b.w. in male and female SD rats. In repeated doses of SKM for 90 days, the administration of 22.5, 45, and 90 mg/kg b.w. per day of the SKM product to female SD rats did not affect clinical signs, body weight, food and water consumption, hematological parameters, clinical chemical parameters, urinalysis, relative organ weights, and gross pathological and histopathological features compared with the control group. Conclusion: Analyses of these results suggest that the long-term oral administration of the SKM product for 90 days does not cause subchronic toxicity.

Terpenoid-lupeol of red dragon fruit (Hylocereus polyrhizus) and its immunomodulatory activity.

Red dragon fruit (Hylocereus polyrhizus, (F.A.C. Weber) Britton and Rose) has been reported to have various biological activities such as antimicrobial, anti-hypercholesterolemia, anti-diabetes mellitus, cardiovascular risk reduction, health supplement, and melanoma cell inhibitory. The red thick peel of this fruit is just practically a waste that is possibly utilized to maintain health, therefore this research aimed to isolate and identify active compounds of H. Polyrhizus peels which can improve the immune system of body. In order to simplify methanol extract was partition and fractionation. The active compounds of petroleum ether fraction were separated and purified using preparative thin layer chromatography. The identification of the compounds structure was conducted through spectroscopic techniques, including UV, FT-IR, 13CNMR and 1HNMR spectroscopy. The data of spectra revealed that the isolate is lupeol. The statistical analysis of macrophage activity showed that the isolate with concentrations of 100, 50, 25, 12.5 and 6.25µg/mL could activate the macrophages higher than control negative. Terpenoid generated from the isolation of Hylocereus polyrhizus was identified as lupeol (1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-eicosahydrocyclopenya [α] chrysen-9ol. In vitro test shows that the isolated compound had an immunomodulatory activity by increases macrophage phagocytosis of latex beads.

Immunomodulatory Effects of Ethanolic Extract of Thyphonium flagelliforme (Lodd) Blume in Rats Induced by Cyclophosphamide.

The present study aimed to examine the immunomodulatory effect of ethanolic extract of Typhonium flagelliforme (Lodd) Blume in cyclophosphamide-treated rats. The immunomodulatory effects were determined by lymphocytes proliferation, phagocytic activity of macrophages, plasma cytokines of tumor necrosis factor-α, interleukin-1α, interleukin-10 levels, and killer T cells (CD8+ T cells) counts. The results showed that the administration of ethanolic extract of T flagelliforme reduced immunosupessive effect on lymphocyte proliferation, increase the number and phagocytic activity of macrophages in cyclophosphamide-treated rats. Moreover, the ethanolic extract of T flagelliforme also significantly (P < .05) improved the immune system activities especially the proliferation of CD8+T cells and reduced the suppressive effects on cytokines such as tumor necrosis factor-α and interleukin-1α. In conclusion, the ethanolic extract of T flagelliforme has immunomodulatory properties in cyclophosphamide-treated rats. The results suggest that T flagelliforme can reduce immunosuppresive effect caused by a chemotherapeutic agent.

Curcumin and its analogues (PGV-0 and PGV-1) enhance sensitivity of resistant MCF-7 cells to doxorubicin through inhibition of HER2 and NF-kB activation.

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of 80 µM, 21 µM, and 82 µM respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF- kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

Antiproliferative effect of gynura procumbens (lour.) Merr. Leaves etanolic extract on 7,12-dimethylbenz(a)antracene induced male rat liver.

PURPOSE: The leaves of Gynura procumbens (Lour.) Merr. has been traditionally used as anticancer. Ethanolic extract of G. procumbens leaves (EGP) showed cytotoxic activity and anticancer activity in animal cancer model. This study was conducted to observe antiproliferative effect using male rat's liver cells induced by 7,12-dimethylbenz(a)antracene (DMBA). METHODS: Forty days old Sprague Dawley male rats were divided into 4 groups, (1) 0.5 % CMC Na, (2) 20 mg/kg BW DMBA p.o ten times in three weeks, (3) DMBA+300 mg/kg BW of EGP, and (4) DMBA+750 mg/kg BW of EGP. The extract was dissolved into 0.5 % CMC-and administered daily per oral one week before, during and terminated 1 week after the DMBA induction. After sixthteen week experiment, rat livers were sectioned and stained with Haematoxyllene and Eosin (H&E) and AgNOR. RESULTS: Histopatology profile showed no primary liver tumor on DMBA group. mAgNOR value of DMBA+300 mg/kg BW EGP showed significant antiproliferative effect compared to DMBA group. CONCLUSION: Ethanolic extract of G. procumbens leaves showed antiproliferative activity on male rats liver induced by DMBA.