N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells.

Protein kinase dysregulation induces cancer cell aggressiveness leading to rapid tumor progression and poor prognosis in TNBC patients. Many small-molecule kinase inhibitors have been tested in clinical trials to treat TNBC patients. In the previous study, we found that N-phenylpyrazoline small molecule acts as a protein kinase inhibitor in cervical cancer cells. However, there remains unknown about N-phenyl pyrazoline potency as a kinase inhibitor and its anti-cancer activity in TNBC cells. In this study, we investigated the activity of N-phenyl pyrazoline against TNBC cells via tyrosine kinase inhibition. Based on the MTT assay, the IC50 values for the N-phenyl pyrazoline 2, 5, A, B, C, and D against Hs578T were 12.63 µM, 3.95 µM, not available, 18.62 µM, 30.13 µM, and 26.79 µM, respectively. While only P5 exhibited the IC50 against MDA MB 231 (21.55 µM). Further, N-phenyl pyrazoline 5 treatment significantly inhibited the cell proliferation rate of Hs578T and MDA MB 231 cells. The migration assay showed that treatment with the compound N-phenyl pyrazoline 5 with 4 µM concentration significantly reduced cell migration of Hs578T cells. N-phenyl pyrazoline 5 treatment at 1 µM and 2 µM was able to reduce the tumorsphere size of Hs578t cells. A combination treatment of P5 and paclitaxel showed a synergistic effect with a combination index score > 1 in both TNBC cells. Further, the P5 predictively targeted the protein kinases that significantly correlated to breast cancer prognosis. The GSEA analysis result shows that receptor tyrosine kinase, Notch3, Notch4, and Ephrin signaling pathways were targeted by P5. The P5 treatment reduced the EGFR expression level and activation in TNBC cells.

Pyrazoline B-Paclitaxel or Doxorubicin Combination Drugs Show Synergistic Activity Against Cancer Cells: In silico Study.

Background: Multidrug resistance in various cancer types is a major obstacle in cancer treatment. The concept of a single drug molecular target often causes treatment failure due to the complexity of the cellular processes. Therefore, combination chemotherapy, in which two or more anticancer drugs are co-administered, can overcome this problem because it potentially have synergistic efficacy besides reducing resistance, and drug doses. Previously, we reported that pyrazoline B had promising anticancer activity in both in silico and in vitro studies. To increase the efficacy of this drug, co-administration with established anticancer drugs such as doxorubicin and paclitaxel is necessary. Materials and Methods: In this study, we used an in silico approach to predict the synergistic effect of pyrazoline B with paclitaxel or doxorubicin using various computational frameworks and compared the results with those of an established study on the combination of doxorubicin-cyclophosphamide and paclitaxel-ascorbic acid. Results and Discussion: Drug interaction analysis showed the combination was safe with no contraindications or side effects. Furthermore, molecular docking studies revealed that doxorubicin-pyrazoline B and doxorubicin-cyclophosphamide may synergistically inhibit cancer cell proliferation by inhibiting the binding of topoisomerase I to the DNA chain. Moreover, the combination of pyrazoline B-paclitaxel may has synergistic activity to cause apoptosis by inhibiting Bcl2 binding to the Bax fragment or inhibiting cell division by inhibiting α-ß tubulin disintegration. Paclitaxel-ascorbic acid had a synergistic effect on the inhibition of α-ß tubulin disintegration. Conclusion: The results show that this combination is promising for further in vitro and in vivo studies.

Cardioprotective Effect of Hydroalcohol Extract of Andaliman (Zanthoxylum acanthopodium DC.) Fruits on Doxorubicin-Induced Rats.

Andaliman (Zanthoxylum acanthopodium DC.) fruit is a spice plant widely used in North Sumatra. The chemical content in the Andaliman plant has a cardioprotective effect, with antioxidant properties that inhibit oxidative stress and free radicals. SOD (superoxide dismutase), BNP (Brain Natriuretic Peptide), and cTnT (troponin T) are measured as markers of heart damage, and histopathology is to see heart damage. Quercetin administration was used as a comparison. The hydroalcoholic extract's phytochemical content and chemical elements were analyzed using LC-HRMS and GC-MS. The findings showed that the hydroalcohol extract of Andaliman fruits affected the blood levels of SOD, BNP, and cTnT in the blood of doxorubicin-induced rats. SOD levels increased, and BNP decreased; the 300 mg/kg BW group was not significantly different from the 50 mg/kg BW quercetin group. cTnT levels also decreased; the 150 mg/kg BW and 300 mg/kg BW groups were not significantly different, and both were better than the 50 mg/kg BW quercetin group. EAF with 150 mg/kg BW and 300 mg/kg BW can also repair damage to rat heart tissue caused by doxorubicin. Andaliman fruit extract has cardioprotective effects and anti-free radical activity due to its content and potential to be developed.

Synergistic Antibacterial Effect of Ethyl Acetate Fraction of Vernonia amygdalina Delile Leaves with Tetracycline against Clinical Isolate Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

Multidrug-resistant bacteria have raised global concern about the inability to fight deadly infectious diseases. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the most common resistant bacteria that are causing hospital infections. The present study was undertaken to investigate the synergistic antibacterial effect of the ethyl acetate fraction of Vernonia amygdalina Delile leaves (EAFVA) with tetracycline against the clinical isolates MRSA and P. aeruginosa. Microdilution was used to establish the minimum inhibitory concentration (MIC). A checkerboard assay was conducted for the interaction effect. Bacteriolysis, staphyloxanthin, and a swarming motility assay were also investigated. EAFVA exhibited antibacterial activity against MRSA and P. aeruginosa with a MIC value of 125 µg/mL. Tetracycline showed antibacterial activity against MRSA and P. aeruginosa with MIC values of 15.62 and 31.25 µg/mL, respectively. The interaction between EAFVA and tetracycline showed a synergistic effect against MRSA and P. aeruginosa with a Fractional Inhibitory Concentration Index (FICI) of 0.375 and 0.31, respectively. The combination of EAFVA and tetracycline induced the alteration of MRSA and P. aeruginosa, leading to cell death. Moreover, EAFVA also inhibited the quorum sensing system in MRSA and P. aeruginosa. The results revealed that EAFVA enhanced the antibacterial activity of tetracycline against MRSA and P. aeruginosa. This extract also regulated the quorum sensing system in the tested bacteria.

A Literature Review of Artocarpus lacucha Focusing on the Phytochemical Constituents and Pharmacological Properties of the Plant.

Studies have shown that approximately two-thirds of the plant species in the world have some medicinal value. Artocarpus lakoocha is a synonym for Artocarpus lacucha and is a plant that can be found in Indonesia. This medicinal plant has been used to treat many diseases. (1) Objective: This article discusses the scientific investigations carried out on A. lacucha, namely the plant's chemical content, pharmacological activity, and active compounds. (2) Methods: The design of this study was based on an article that was a review of previous research. A search for relevant publications over the past ten years (2012-2022) using data from Pubmed, Proquest, Ebsco, ScienceDirect, and Google Scholar resulted in the discovery of 369 articles. (3) Results: Fifty relevant articles investigate A. lacucha's substances and their applications in the health field. The presence of secondary metabolites and bioactive compounds has been reported, which is evidence that A. lacucha possesses antidiarrheal, immunostimulant, anticholesterol, and hepatoprotective agents. (4) Conclusions: Mobe (A. lacucha) is a plant native to North Sumatra, Indonesia. This plant is efficacious as an antioxidant, antibacterial, antidiarrheal, anti-inflammatory, analgesic, antinociceptive, schistosomicidal, hepatoprotective, neuroprotective, cytotoxic, antiglycation, and anticholesterol, and can also be used for anti-aging and wound healing. In addition to its various benefits, it turns out that this plant also has many active compounds that are useful to the health sector, especially the pharmaceutical field.

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review.

Doxorubicin is a widely used and promising anticancer drug; however, a severe dose-dependent cardiotoxicity hampers its therapeutic value. Doxorubicin may cause acute and chronic issues, depending on the duration of toxicity. In clinical practice, the accumulative toxic dose is up to 400 mg/m2 and increasing the dose will increase the probability of cardiac toxicity. Several molecular mechanisms underlying the pathogenesis of doxorubicin cardiotoxicity have been proposed, including oxidative stress, topoisomerase beta II inhibition, mitochondrial dysfunction, Ca2+ homeostasis dysregulation, intracellular iron accumulation, ensuing cell death (apoptosis and necrosis), autophagy, and myofibrillar disarray and loss. Natural products including flavonoids have been widely studied both in cell, animal, and human models which proves that flavonoids alleviate cardiac toxicity caused by doxorubicin. This review comprehensively summarizes cardioprotective activity flavonoids including quercetin, luteolin, rutin, apigenin, naringenin, and hesperidin against doxorubicin, both in in vitro and in vivo models.

Immunomodulatory effects of standardized extract of Curcuma mangga val. on cytokines, antibody and delayed-type hypersensitivity response in Wistar rats.

BACKGROUND AND PURPOSE: Recently, we have highlighted the immunomodulatory activity of Curcuma mangga Val. on phagocytosis ability. The current study was conducted to determine the immunomodulatory effects of the standardized extract of C. mangga rhizomes by in vitro and in vivo studies. EXPERIMENTAL APPROACH: The C. mangga extract was standardized according to a guideline for herbal preparation. The extract was investigated for its immunomodulatory effects on gene expression of cytokines, cytokines and antibody production as well as delayed-type hypersensitivity (DTH) response. The gene expression of cytokines on lipopolysaccharide-induced-RAW 264.7 cells was analysed by reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of the extract on DTH response was investigated by the paw edema method, meanwhile the effects of the extract on antibody and cytokine production from normal and cyclophosphamide-induced Salmonella typhimurium infected rats were determined using an enzyme-linked immunosorbent assay (ELISA). FINDINGS/RESULTS: The extract of C. mangga demonstrated an inhibitory effect on gene expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α, and IL-6 as compared to lipopolysaccharide-induced cells. The extract also depicted inhibitory activity on IL-4 production as compared to the negative control. Whereas, the DTH response and production of immunoglobulin G from both groups after treatment with C. mangga extract were higher than those of negative control (P < 0.05). CONCLUSION AND IMPLICATIONS: The results indicated that the C. mangga extract has immunomodulatory effects, emphasizing its potential to be developed as immunotherapeutic agent.

Effects of 3% binahong ( Anredera cordifolia) leaf extract gel on alveolar bone healing in post-extraction tooth socket wound in Wistar rats ( Rattus norvegicus).

Background: Binahong ( Anredera cordifolia (Ten.) STEENIS) is a widely available herbal plant in Indonesia and has been intensely researched for its healing abilities due to its biological activities, but few have studied its capability in accelerating hard tissue healing in post-extraction tooth sockets. The purpose of this study was to analyse the effects of 3% binahong leaf extract gel on alveolar bone healing in post-extraction sockets in Wistar rats. Methods: In this study, 48 male Wistar rats were randomly allocated to twelve groups. After the extraction of the left mandibular incisor, sockets in Group I to IV were given 3% binahong leaf extract gel, group V to VIII were given a control gel, and group IX to XII were given Gengigel ® for 14 days. The residual socket volume (RSV) and fibroblast proliferation were observed on the 3 rd, 7 th, and 14 th day post-extraction, while the osteoblast and osteocyte proliferation were observed on the 7 th, 14 th, and 28 th day post-extraction. The RSV data were analysed using repeated measure ANOVA and one-way ANOVA, while the histopathological data were analysed using one-way ANOVA. Results: The results showed that the binahong group had the lowest RSV and the highest fibroblast proliferation compared to the other groups on the 7th day (p<0.05) and the highest osteoblast and osteocyte proliferation compared to the other groups on the 14 th day (p<0.05). Conclusion: The experiment showed that 3% binahong leaf extract gel could accelerate wound closure, which was characterized by a greater decrease in the RSV value in comparison to the other treatment groups and could enhance alveolar bone healing by increasing the proliferation of fibroblasts, osteoblasts, and osteocytes.

The anticancer activities of Vernonia amygdalina Delile. Leaves on 4T1 breast cancer cells through phosphoinositide 3-kinase (PI3K) pathway.

Vernonia amygdalina Delile (Asteraceae) is used in traditional medicine to treat diabetes mellitus, and some research provides its activity to treat breast cancer. The aim of this study is to assess the anticancer activity of Vernonia amygdalina Delile leaves fractions on 4T1 breast cancer cells. Analysis of phytochemical compounds were carried out with LC-MS/MS. Cytotoxic activity was determined using the MTT method in the 4T1 cell line. Apoptosis, the cell cycle, and PI3K and mTOR profiles were analyzed with flow cytometry. The phytochemicals found were diterpene (ingenol-3-angelate) and some phenolics (chlorogenic acid and 4-methoxycinnamic acid), flavonoids (apigetrin, apigenin, luteolin, diosmetin, baicalin, rhoifolin, and scutellarin), and coumarines (7-hydroxycoumarine, 4-methylumbelliferone, and 4-methylumbelliferyl glucuronide). The results of the MTT assay showed that the IC50 values n-hexane fraction, ethylacetate fraction (EAF), and ethanol fractions were 1,860.54 ± 93.11, 25.04 ± 0.36, and 1,940.84 ± 96.37 µg/mL, respectively. EAF induced early and late apoptosis, inhibited cell cycle progression on the G2/M phase, and inhibited PI3K and mTOR expression. The EAF of Vernonia amygdalina Delile leaves showed anticancer activity on 4T1 breast cancer cells through induction of apoptosis, enhanced cell accumulation on G2/M phases in the cell cycle, and inhibited expression of PI3K and mTOR.

Differences in dental arch characteristics between genders in patients with suspected condylar hyperplasia in a North Sumatra subpopulation: a cross-sectional study.

Background: Condylar Hyperplasia (CH) is a self-limiting mandibular condyle disorder that shows asymmetry progress conjunction with associated occlusal changes as long as condylar growth is still active and leads to facial asymmetry. This study aimed to evaluate dental arches by analyzing dental arch asymmetry and form in orthodontic patients with CH in a North Sumatra subpopulation. Methods: This is a retrospective study of suspected CH patient's clinical records who sought for the initial orthodontic treatment between January 2015 to March 2019. Patient with facial asymmetry (based on photography, posterior cross bite and midline deviation), positive temporomandibular joint disorder in functional analysis, and no history of facial trauma were included in the study. Dental arch asymmetry was based on the measurement of dental midline deviation, canine tip in the dental arch, distance of the upper canines from the palatal suture, and inter canine distance. The evaluation of dental arch was achieved by comparing arch width and length. Results: There was a significant difference (p<0.05) of upper canine distance from the palatal suture in female patients when evaluating upper dental arch asymmetry. There was a moderate correlation (r=0.379) in midline deviation between upper and lower dental arch. The dimension and dental arch form was mid and flat, and there was moderate correlation (r=0.448) between the upper and lower dental arch form in these CH patients. Conclusion: The evaluation of dental arch symmetry and arch form showed asymmetric occlusal characteristics in orthodontics patient with CH in North Sumatera subpopulation. In treating these patients, we recommend the plaster cast evaluation as essential and routine procedure in order to understand the complexity of occlusal change due to active growth of condylar and limitation in radiography evaluation.

The PI3KCA and AKT Inhibitory Activities of Litsea Cubeba Lour. Fruits and Heartwoods Towards Hela Cells.

AIM: To investigated the activities of chloroform fractions at pH 7 of Litsea cubeba Lour. Fruits and heartwoods (CF-7F and CF-7H) in decrease expression of PI3KCA, Akt-1 and Akt-2 genes towards cervical cancer cell culture (HeLa) experiments in vitro. MATERIAL AND METHODS: CF-7F and CF-7H (12.5 and 25 µg/mL) were tested for its potential inhibition on gene expression of PI3KCA, Akt-1 and Akt-2 genes by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method. RESULT: CF-7F and CF-7H were showed the activity to reduce the expression of PI3KCA, Akt-1 and Akt-2 genes. CONCLUSION: Our results suggest that CF-7F and CF-7H significantly inhibit the expression of PI3KCA, Akt-1 and Akt-2 genes.

Cell Cycle Inhibition of Ethylacetate Fraction of Zanthoxylum Acanthopodium DC. Fruit against T47D Cells.

BACKGROUND: The use of medicinal plants is increasing in several decades for relief many diseases. Indonesia consists of thousands of islands with various plants and the manners of the community using plants as a treatment for every disease traditionally. AIM: Cytotoxic activity of ethyl acetate fraction (EAF) of Zanthoxylum acanthopodium fruit was tested towards T47D breast cancer cells. METHODS: The in vitro cytotoxic activity was performed by MTT assay, and the result was expressed as the IC50 (Inhibitory Concentration), and cell cycle inhibition was investigated by flow cytometry to assess the inhibition in every phase of cell cycle, and the role of expression cyclin D1 and p53 in cell cycle inhibition were performed by immunocytochemistry. RESULTS: EAF was showed to have high activity with a value of IC50 48.94 ± 0.32 µg/mL. EAF of 25 µg/mL caused cell accumulation at G0/G1 (60.48%) and in a control cell (51.69%) and decreased expression of cyclin D1 and increased expression of p53. CONCLUSION: The results obtained in this study provided scientific support for further investigation on compounds in Z. acanthopodium fruit which in the future could be used for medication.

The Immunomodulatory Activities of Picria Fel-Terrae Lour Herbs towards RAW 264.7 Cells.

AIM: To investigate immunomodulatory activities of Picria fel-terrae Lour herbs extract against inflammatory biomarkers by conducting cell culture experiments. MATERIAL AND METHODS: The herbs of Picria fel-terrae Lour were dried and extracted with n-hexane, ethyl acetate, 96% ethanol, followed by evaporation and freeze-drying. Phytochemicals screening were analysed with thin layer chromatography method. Cell viability was assessed with MTT assay. The genes of Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-6, interleukin (IL)-1ß and inducible Nitric Oxide Synthase (iNOS), Cyclooxygenase (COX-2) in lipopolysaccharide (LPS)-induced macrophages were analysed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method. RESULTS: Phytochemicals screening showed the presence of steroids in n-hexane extract (ENPFH) and flavonoids, glycosides, saponins, tannins in ethyl acetate (EEAPFH) and ethanol (EEPFH) extracts. The Viability of RAW 264.7 cell toward ENPFH, EEAPFH, and EEPFH (1-200 µgmL-1) showed no toxicity effects. At the gene level, ENPFH; EEAPFH; EEPFH decreased the gene expression of TNF-α, IL-6, IL-1ß, iNOS, and COX-2 which induced with LPS (1 µgmL-1). CONCLUSIONS: Our results suggest that extracts of Picria fel-terrae Lour Herbs possesses immunomodulatory activities by inhibiting selected inflammatory biomarkers at the gene levels in LPS-induced macrophages.

The Activity of Hydrolyzed Virgin Coconut Oil to Increase Proliferation and Cyclooxygenase-2 Expression towards on NIH 3T3 Cell Line in Wound Healing Process.

AIM: This study aims to determine the effect of hydrolysed virgin coconut oil (HVCO) to increase cell proliferation, COX-2 expression of NIH 3T3. METHODS: The sample used was Virgin Coconut Oil (VCO). VCO was partially hydrolysed using lipase from Rhizomucor miehei (active on sn-1,3 position) to produce hydrolysed VCO (HVCO) composed of free fatty acids, 2-monoglycerides. Then acid value was determined. The effect of HVCO on proliferation was evaluated using the MTT method. Wound healing assay was established by a cell migration method, and COX-2 expression was determined using RT-PCR. RESULTS: Acid value is 135.89 ± 0.12 mg NaOH/g oil and free fatty acids (FFA) is 48.50 ± 0.06%. The effect of HVCO 62.5 µg/mL on cell proliferation after 24h, 48h, and 72h incubation found as viable cells are 109.24 ± 0.52%; 118.26 ± 0.91% and 106.59 ± 0.74%. Percent of wound closed after 24 h and 48 h incubation are 69.94 ± 0.54% and 100.00 ± 0.00%, and expression of COX-2 increased from 1 (control) to 1.83 (HVCO). CONCLUSION: The results suggest that HVCO is effective to increase cells proliferation and hence wound healing process.

The Role of Coconut Oil to Increase Expression of MMP-9, PDGF-BB, and TGF-ß1 in NIH-3T3 Cell Line.

AIM: The objective of the study was to evaluate protein expression in NIH 3T3 cells that are treated with virgin coconut oil (VCO) and hydrolysed of virgin coconut oil (HVCO) in vitro. METHODS: Coconut oil used in this study was virgin coconut oil (VCO) and VCO hydrolysed by Rhizomucor miehei (HVCO). NIH 3T3 cells (5x105 cells/well) were seeded in nine wells and incubated for overnight, then divided into three groups. Each group consisted of three wells. Group one without treatment, group two added VCO, and group three added HVCO and then incubated for overnight. One well in each group was added MMP-9, PDGF-BB, and TGF-ß1 and incubated one hour. Finally, expressions of MMP-9, PDGF-BB, and TGF-ß1 were detected using immunocytochemistry method. RESULTS: The results of the study showed that VCO and HVCO increased protein expressions of MMP-9, PDGF-BB, and TGF-ß1. Percentage of MMP-9 expressions treated by VCO increased from 2.89 ± 0.07 to 28.16 ± 0.34, PDGF-BB from 28.11 ± 0.13 to 48.53 ± 0.49, and TGF-ß1 from 4.19 ± 0.08 to 18.41 ± 0.54. Percentage of MMP-9 expressions treated by HVCO increased from 2.89 ± 0.07 to 55.40 ± 0.94, PDGF-BB from 28.11 ± 0.13 to 61.65 ± 0.42, and TGF-ß1 from 4.19 ± 0.08 to 36.35 ± 0.67. CONCLUSION: VCO and HVCO increase the expression of MMP-9, PDGF-BB, dan TGF-ß1 in NIH3T3 cells and therefore, coconut oil active in the wound healing process. HVCO is more than active than VCO.

The Inhibitory Activity of Picria fel-terrae Lour Herbs Extract on Nitric Oxide Production toward RAW 264.7 Cells Induced by Lipopolysaccharide.

AIM: The objective of this study was to evaluate the inhibitory activity of Picria fel-terrae Lour on Nitric Oxide production toward RAW 264.7 cells. METHODS: The extraction was obtained by maceration method using n-hexane, ethyl acetate and ethanol solvents and then nitric oxide (NO) production was obtained using Griess reagent. RESULTS: Extract of Picria fel-terrae Lour herbs can reduce the NO production toward RAW 264.7 cells with induced by lipopolysaccharide has obtained nitric concentrations 12.5 and 25 µg/mL from n-hexane extract (72.50 ± 4.51 and 10.42 ± 1.82), ethyl acetate extract: (88.33 ± 6.51 and 30.83 ± 6.86), ethanol extract: (75.00 ± 1.91 and 22.08 ± 2.53). CONCLUSION: n-hexane extract of Picria fel-terrae Lour Herbs has a high potential to reduce the NO production in LPS-stimulated RAW 264.7 cells compared to ethyl acetate and ethanol extracts of Picria fel-terrae Lour Herbs.

Effect of Saurauia vulcani Korth. Leaves on Superoxide Dismutase, HbA1c Levels and Insulin Expression in Hyperglycemic Rats.

AIM: This study aimed to investigate Saurauia vulcani Korth. leaves. the activity of ethanol extract in hypoglycemic, superoxide dismutase (SOD), glycosylated haemoglobin (HbA1c) and detection of insulin expression by immunochemistry. METHODS: Saurauia vulcani Korth. Leaves powder was extracted by maceration method with ethanol 96%. The extract was administrated orally in doses of 100 mg/kg BW for 27 days. Diabetes was induced in rats by administered of Nicotinamide (NA) 230 mg/kg BW and streptozotocin (STZ) 65 mg/kg BW. Level of blood glucose, SOD, HbA1c were measured, and histopathology pancreas was observed to determine insulin expression with immunochemistry. RESULTS: Ethanol extract of Saurauia vulcani Korth. Leaves (EESL) shown a significantly (*p < 0.05) reduced in blood glucose levels at 104.25 ± 2.562 mg/dL and HbA1c level at 32.53 ± 0.188 ng/mL, but increased SOD level at 60.64 ± 0.740 pg/mL and histopathology study shown secretion insulin as seen number of expressions of insulin / slice 31.00 ± 0.315. CONCLUSION: The result of this study showed EESL possess the hypoglycemic activity and increase the level of SOD but decrease the level of HbA1c in diabetic rat condition. The mechanism of the activity is suggested by stimulating the insulin secretion of pancreas ß-cells which were damaged.

Evaluation of Cytotoxic Activity Alkaloid Fractions of Zanthoxylum acanthopodium DC. Fruits.

AIM: This study was carried out to investigate cytotoxic activity towards T47D, 4T1, MCF-7, HeLa, and Raji cells of alkaloid fractions of Zanthoxylum acanthopodium DC. fruits. Zanthoxylum acanthopodium DC. METHODS: The fruit was extracted by maceration. The ethanol extract was fractionated with liquid-liquid extraction using n-hexane, chloroform at pH 3, 7, and 9 to obtained alkaloid fractions. Cytotoxic activity for fraction chloroform at pH 7 and 9 was determined with MTT assay. RESULTS: The IC50 of fraction chloroform at pH 7 and 9 was (92.67 ± 1.37; 71.87 ± 1.04; 159.87 ± 0.63; 123.39 ± 0.81; and 103.09 ± 0.58 µg/mLfor pH 7) and (451.29 ± 25.48; 247.18 ± 2.82; 318.46 ± 5.40; 303.96 ± 8.75; and 181.45 ± 1.35 µg/mL for pH 9) respectively. CONCLUSION: The results reveal that alkaloid fractions at pH 7 and 9 of Zanthoxylum acanthopodium DC. Fruits have cytotoxic activity. Our further study is to isolate and assesses anticancer activity from alkaloid compounds.

Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) Modulates TCD4+ and TCD8+ Cell Profile of Doxorubicin-Induced Immuno-Suppressed Rats.

AIM: To evaluate the immunomodulatory effects of ethanolic extract of herb pugun tanoh on TCD4 and TCD8 cells in Doxorubicin-induced rats. METHODS: Fifteen male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, DOX-treated rats (4.67 mg/kg BW body weight on day 1 and 4) and were administered normal saline 0.9% orally once daily for 7 consecutive days, Group 2, receiving Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) of dose 150 mg/kg BW orally, Group 3, receiving dose Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) 300 mg/kg BW orally. The rats of group 2-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1-4 to suppress immune functions. RESULTS: Treatment of 300 mg/kg BW of Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) succeeded in reducing side effect doxorubicin based on increasing the TCD4+ and TCD8+ blood level. CONCLUSION: Ethanolic Extract of Herb Pugun Tanoh (Picria fel-terrae Lour.) could increase the level of TCD4+ and TCD8+ in rats which induced by doxorubicin.

Characterisation of Lactic Acid Bacteria from Dengke Naniura of Common Carp (Cyprinus carpio) with α-Glucosidase Inhibitory Activity.

BACKGROUND: Fermented foods were favourable because of its properties in enhancing the shelf life, safety, function, sensory and nutrition. There are many fermented foods tested in vitro as an α-glucosidase enzyme inhibitor. Dengke naniura is one of Indonesia's traditional food made using fermentation. AIM: To identify lactic acid bacteria (LAB) strains in dengke naniura and its properties in inhibiting the α-glucosidase enzyme. METHODS: The carp were sacrificed, and soaked with rough lemon for 6 hours then spices added to it for another 1 hour. Then the isolation of LAB conducted using a serial dilution of the samples. The selected isolates of the LAB were then characterised by its morphology under the microscope, gram staining, growth at 15°C and 45°C and biochemical identification. The isolates were then tested for its inhibiting properties against the α-glucosidase enzyme. RESULTS: The isolates (DL-109 and DL-107) were a gram-positive, nonspore-forming and non-motile rod. The Physiological and biochemical properties of the isolates confirm its LAB properties. On the test against α-glucosidase enzyme activity inhibition, isolate DL-109 LAB (4) showed dominant activity with very low IC50 compared to Acarbose (IC50 = 128.06 ppm) and DL-107 (46.32 ppm) while at the lowest dosage of 25 µg/ml DL-109 showed activity as much as 54.76%. CONCLUSION: These findings concluded that the isolates were LAB by its properties and can be used for lowering blood glucose in term of inhibition of the α-glucosidase enzyme.