Potential antiaging activity of secretome gel of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) in UV-induced mice models.

Objectives: Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model. Materials and Methods: The secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice's dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-ß1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (P<0.05). Results: UVB induction caused loss of collagen, increasing inflammation and high expression of aging mediators. SC increased the gene expression of TGF-ß1 and IL-10 and decreased IL-18 gene expression. Histopathological tests showed that SG increased collagen density, lowered inflammation, and repaired cell damage in skin tissue. Immunohistochemistry test showed that SC decreased MMP-2, MMP-13, and P53 expression, in contrast, increased COL4A1. Conclusion: The secretome gel of hWJ-MSCs showed antiaging activities with potential for preventing and curing skin aging.

Green Tea Extract Reduced Lipopolysaccharide-Induced Inflammation in L2 Cells as Acute Respiratory Distress Syndrome Model Through Genes and Cytokine Pro-Inflammatory.

Background: Acute Respiratory Distress Syndrome (ARDS) is a severe lung inflammatory condition that has the capacity to impair gas exchange and lead to hypoxemia. This condition is found to have been one of the most prevalent in patients of COVID-19 with a more serious condition. Green tea (Camellia sinensis L.) contains polyphenols that possess many health benefits. The purpose of this study was to assess the anti-inflammatory activities of green tea extract in Lipopolysaccharide (LPS)-induced lung cells as ARDS cells model. Methods: In this study, rat lung cells (L2) were induced by LPS to mimic the inflammation observed in ARDS and later treated with green tea extract. Pro-inflammatory cytokines such as Interleukin (IL)-12, C-Reactive Protein (CRP) as well as Tumor Necrosis Factor-α (TNF-α) were investigated using the ELISA method. Gene expression of NOD-Like Receptor Protein 3 (NLRP-3), Receptor for Advanced Glycation End-product (RAGE), Toll-like Receptor-4 (TLR-4), and Nuclear Factor-kappa B (NF-κB) were evaluated by qRTPCR. Apoptotic cells were measured using flow cytometry. Results: The results showed that green tea extract treatment can reduce inflammation by suppressing gene expressions of NF-κB, NLRP-3, TLR-4, and RAGE, as well as pro-inflammatory cytokines such as IL-12, TNF-α, and CRP, an acute phase protein. Apoptosis levels of inflamed cells also found to be lowered when green tea extract was administered; thus, also increasing live cells compared to non-treated cells. Conclusion: These findings could lead to the future development of supplements from green tea to help alleviate ARDS symptoms, especially during critical moments such as the current pandemic.

Antidiabetic and hepatoprotection effect of butterfly pea flower (Clitoria ternatea L.) through antioxidant, anti-inflammatory, lower LDH, ACP, AST, and ALT on diabetes mellitus and dyslipidemia rat.

This study explores the antidiabetic and hepatoprotective potential of Butterfly pea flower extract (Clitoria ternatea L.) (CTE) in diabetic and dyslipidemia rat models. Diabetes Mellitus (DM) is a chronic metabolic disorder marked by high levels of blood glucose, which can cause dyslipidemia and liver damage as a result of oxidative stress. CTE, a natural substance, is recognized for its positive attributes, such as anti-inflammatory, antioxidant, anti-diabetic, anti-dyslipidemia, antibiotic, and liver tissue protection capabilities. Dyslipidemia was induced in rats using a high-fat diet (HFD) and propylthiouracil (PTU) for 28 days. DM was induced using streptozotocin (STZ) and nicotinamide (NA). Rats were treated with varying doses of CTE for 28 days, along with glibenclamide and simvastatin. The research showed that CTE raised the levels of SOD, CAT, and liver proteins while lowering the levels of MDA, LDH, ACP, AST, ALT, IL-1ß, and CRP in rats with DM and dyslipidemia. This suggests that CTE might be useful for treating DM.

hWJMSCs inhibit inflammation and apoptosis in an ARDS cell model.

Acute respiratory distress syndrome (ARDS) is a type of lung failure caused by fluids and hypoxemia. Mesenchymal stem cells (MSCs) have been shown to decrease levels of pro-inflammatory mediators and inflammatory cells. These cells have anti-inflammatory, anti-apoptotic, and anti-microbial activity, and protect against lung injury. Objective: This research evaluated the potential of human Wharton's jelly MSCs (hWJMSCs) to inhibit inflammation and apoptosis in lipopolysaccharide (LPS)-induced rat lung cells (L2). Methods: hWJMSC treatment in LPS-induced rat lung cells was performed with 1:1, 1:5, 1:10, or 1:25 ratios of hWJMSCs to L2 cells. The gene expression of angiotensin-converting enzyme-2 (ACE-2), receptor for advanced glycation end products (RAGE), nuclear factor kappa B (NFκB), and C-X-C motif chemokine ligand-9 (CXCL-9) was quantified with RT-PCR, and the levels of C-reactive protein (CRP), interleukin-12 (IL-12), and tumor necrosis factor-alpha (TNF-α) were measured with ELISA. Results: hWJMSCs increased ACE-2 gene expression, and decreased CXCL-9, NFκB, and RAGE gene expression. The treatment also suppressed CRP, TNF-α, and IL-12 levels, and increased the percentage of live cells, but decreased the percentages of necrotic cells and apoptotic cells in inflammatory rat lung cells, which served as an ARDS cell model. Conclusion: Co-culture of hWJMSCs and L2 cells mitigated inflammation through increasing ACE-2 gene expression, and decreasing CXCL-9, NFκB, and RAGE gene expression; decreasing TNF-α and CRP protein levels; and decreasing necrosis, and early and late apoptosis. A co-culture ratio of 1:1 was most effective.

Protective effect of yacon leaves extract (Smallanthus sonchifolius (Poepp.) H. Rob) through antifibrosis, anti-inflammatory, and antioxidant mechanisms toward diabetic nephropathy.

Background and purpose: Diabetic nephropathy (DN) is a chronic kidney failure, which may lead to fatality. Mesangial cell proliferation, renal inflammation, stress oxidative, and fibrosis are involved in DN progression. Yacon leaves (Smallanthus sonchifolius (Poepp.) H. Rob.) contains large amounts of phenolic compounds and it has the ability to inhibit oxidative stress, inflammation, and fibrosis. Considering the potential of yacon leaves extract (YLE), it may be used for DN treatment. This research aimed to elucidate YLE's potential as anti-DN through anti-inflammatory, antioxidant, and antifibrosis mechanisms. Experimental approach: Mesangial cells were induced by glucose 20 mM for 5 days and treated with YLE concentrations as much as 5, 10, and 50 µg/mL. TGF-ß1, TNF-α, and MDA levels were measured using the ELISA method. SMAD2, SMAD3, SMAD4, and SMAD7 gene expressions were analyzed using the qRT-PCR method. Findings/Results: YLE at 5, 10, and 50 µg/mL could reduce the levels of TGF-ß1, TNF-α, and MDA compared with the DN cells model. YLE could reduce gene expressions of SMAD2, SMAD3, and SMAD4 and increase SMAD7 expression. Conclusion and implications: YLE potentially mitigated diabetic nephropathy through antifibrosis, anti-inflammatory, and antioxidant capacities.

Inflammation inhibitory activity of green tea, soybean, and guava extracts during Sars-Cov-2 infection through TNF protein in cytokine storm.

Coronavirus disease is caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) known as COVID-19. COVID-19 has caused the deaths of 6,541,936 people worldwide as of September 27th, 2022. SARS-CoV-2 severity is determined by a cytokine storm condition, in which the innate immune system creates an unregulated and excessive production of pro-inflammatory such IL-1, IL-6, NF Kappa B, and TNF alpha signaling molecules known as cytokines. The patient died due to respiratory organ failure and an acute complication because of the hyper-inflammation phenomenon. Green tea, soybean, and guava bioactive substances are well-known to act as anti-inflammation, and antioxidants become prospective COVID-19 illness candidates to overcome the cytokine storm. Our research aims to discover the bioactivity, bioavailability, and protein targets of green tea, soybean, and guava bioactive compounds as anti-inflammatory agents via the TNF inhibition pathway. The experiment uses in silico methods and harnesses the accessible datasets. Samples of 3D structure and SMILE identity of bioactive compounds were retrieved from the KNApSAck and Dr Duke databases. The QSAR analysis was done by WAY2DRUG web server, while the ADME prediction was performed using SWISSADME web server, following the Lipinsky rules of drugs. The target protein and protein-protein interaction were analyzed using STRING DB and Cytoscape software. Lastly, molecular docking was performed using Autodock 4.2 and visualization with BioVia Discovery Studio 2019. The identified study showed the potential of green tea, soybean, and guava's bioactive compounds have played an important role as anti-inflammation agents through TNF inhibitor pathway.

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-ß1/SMADs pathway.

Background: Chronic kidney disease (CKD) happens due to decreasing kidney function. Inflammation and oxidative stress have been shown to result in the progression of CKD. Quercetin is widely known to have various bioactivities including antioxidant, anticancer, and anti-inflammatory activities. Objective: To evaluate the activity of quercetin to inhibit inflammation, stress oxidative, and fibrosis on CKD cells model (mouse mesangial cells induced by glucose). Methods and Material: The SV40 MES 13 cells were plated in a 6-well plate with cell density at 5,000 cells/well. The medium had been substituted for 3 days with a glucose-induced medium with a concentration of 20 mM. Quercetin was added with 50, 10, and 5 µg/mL concentrations. The negative control was the untreated cell. The levels of TGF-ß1, TNF-α, and MDA were determined using ELISA KIT. The gene expressions of the SMAD7, SMAD3, SMAD2, and SMAD4 were analyzed using qRT-PCR. Results: Glucose can lead to an increase in inflammatory cytokines TNF-α, TGF-ß1, MDA as well as the expressions of the SMAD2, SMAD3, SMAD4, and a decrease in SMAD7. Quercetin caused the reduction of TNF-α, TGF-ß1, MDA as well as the expression of the SMAD2, SMAD3, SMAD4, and increased SMAD7. Conclusion: Quercetin has anti-inflammation, antioxidant, antifibrosis activity in the CKD cells model. Thus, quercetin is a promising substance for CKD therapy and further research is needed to prove this in CKD animal model.

Detam 1 black soybean against cisplatin-induced acute ren failure on rat model via antioxidant, antiinflammatory and antiapoptosis potential.

Background and aim: Cis-Diamminedichloroplatinum (II) (Cisplatin) is one of the most synthetic anticancer drug but have several adverse effects and one of them is acute ren failure. Cisplatin can induce nephrotoxicity occur via the toxic generation of reactive oxygen species (ROS). Black soybean (Glycine max L. Merr.) has been reported contain high levels of phenolics and anthocyanins that has antioxidant activity. This study aims to determine the effect of ethanol extract of black soybean (EEBS) against cisplatin-induced nephrotoxicity in rats. Experimental procedure: Cisplatin-induced nephrotoxicity rats treated with EEBS and the blood samples taken on days 0, 9, and 18. The effects of EEBS was evaluated by determining Interferon-γ (IFN-γ), Caspase-3 (Casp-3), and Interleukin-1ß (IL-1ß) expression using immunohistochemistry (IHC), blood urea nitrogen (BUN), Uric Acid (UA) content and catalase (CAT) content in the blood plasma with colorimetric assay kit. Results and conclusion: Based on the results, EEBS treatment had successfully reduced pro-inflammatory cytokines IL-1ß and IFN-γ, and improved physiological condition by lowering BUN and UA content while increasing CAT activity. No significant effect was found in Casp-3 expression. EEBS has potential to improve acute renal failure condition through inflammatory suppression and renal function improvement.

The effect of mesenchymal stem cell-conditioned medium gel on burn wound healing in rat.

Background and Aim: Stem cells are cells that can proliferate to form a new tissue, leading to its use in regenerative therapy. Stem cells will secrete biological factors, such as growth factors, cytokines, and other proteins to their surroundings and culture medium/conditioned medium (CM), altering tissue physiology. These factors can help wound healing, but their effect on third-degree burns is poorly understood. This research aimed to study the activity of mesenchymal stem cell-conditioned medium gel in healing and repairing third-degree burns on rats skin. Materials and Methods: Twenty-four Sprague-Dawley rats with burn wounds on the dorsal area were divided into four groups; the first group was treated with CM gel, with a concentration equivalent to 0.05% protein, the second group was treated with a placebo gel, the third group with silver sulfadiazine (SSD) cream (SSD-Burnazin contain 10 mg/g SSD), and the fourth group was not given any treatment, for 21 days, and on the final day, the rats were sacrificed, and the skins were taken. All topical treatments completely cover the wound area. Results: Wound healing process indicators observed include wound diameter, scabs' formation, blister formation, and hair growth every day. The skins taken were processed with hematoxylin-eosin and Masson's trichrome staining. The indicators studied include neutrophil infiltration, mononuclear cell infiltration, neovascularization, collagen area, and re-epithelization ratio. Conclusion: CM shows better wound healing than other groups and faster hair growth.

Production of Inflammatory Mediators in Conditioned Medium of Adipose Tissue-Derived Mesenchymal Stem Cells (ATMSC)-Treated Fresh Frozen Plasma.

BACKGROUND Inflammation is the body's first response to an illness that causes irritation or infection. Inflammation is tightly correlated with aging, which is a progressive degenerative process. Conditioned medium (CM) from adipose tissue-derived mesenchymal stem cells (CM-ATMSCs) has been shown to stimulate collagen synthesis and dermal fibroblast migration, as well as reduce wrinkles and improve wound healing. This study aimed to observe the production of inflammatory modulators - interleukin (IL)-1alpha, IL-6, IL-10, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) - in CM-ATMSCs treated with fresh frozen plasma (FFP) at passages 3 (P3), 7, 11, and 15. MATERIAL AND METHODS ATMSCs P3 were obtained from liposuction of female donors, and the CM from ATMSCs was collected. Measurement of these cytokines was performed with ELISA. RESULTS At many passages, IL-6, a proinflammatory modulator, was discovered to be the most powerful modulator among FFP- and non-FFP-treated cells. However, CM-ATMSCs treated with FFP and in the late passage have significant differences (P<0.05) compared to non-FFP treatments and in other passages in their effects on secretion of inflammatory modulators. CONCLUSIONS In conclusion, CM-ATMSC has the potential to secrete proinflammatory modulators.

Decreased Inhibition of Proliferation and Induction of Apoptosis in Breast Cancer Cell Lines (T47D and MCF7) from Treatment with Conditioned Medium Derived from Hypoxia-Treated Wharton's Jelly MSCs Compared with Normoxia-Treated MSCs.

Background : Mesenchymal stem cells (MSCs) are an appealing source of adult stem cells for cell therapy due to the high rate of proliferation, self-renewal capability, and applicable therapy. Wharton's jelly (WJ), the main component of the umbilical cord extracellular matrix, comprises multipotent stem cells with a high proliferation rate and self-renewal capability and has anti-cancer properties. MSCs have been reported to secrete a variety of cytokines that have a cytotoxic effect in various cancers. Oxygen tension affects MSCs proliferation, cytokines level but no in surface markers expression, MSCs' differentiation. We explored the cytotoxic effect and inducing apoptosis of Wharton's jelly derived mesenchymal stem cells (WJMSCs) secretions from normoxic WJMSCs (WJMSCs-norCM) (CM: conditioned medium) and hypoxic WJMSCs (WJMSCs-hypoCM) in breast cancer cell lines (T47D and MCF7). Materials and Methods: Cytotoxic activity was determined using the MTS assay. RT-PCR was performed to measure the expression of apoptosis-inducing genes, specifically P53, BAX, and CASP9, and the antiapoptotic gene BCL-2. Results: WJMSCs-norCM and WJMSCs-hypoCM were potent inhibitors of the proliferation in both cell lines. WJMSCs-norCM had more anticancer activity in T47D and MCF7. The IC50 value of WJMSCs-norCM on MCF7 was 42.34%, and on T47D was 42.36%. WJMSCs-norCM significantly induced the gene expression of apoptotic P53, BAX, and CASP9 and insignificantly decreased the antiapoptotic gene BCL-2 in both MCF7 and T47D cells. WJMSCs-CM has anticancer activity by inducing P53, BAX, and CASP9 apoptotic genes. Conclusion: WJMSCs-norCM has more anticancer activity than WJMSCs-hypoCM.

Anti-inflammatory and antiaging properties of chlorogenic acid on UV-induced fibroblast cell.

BACKGROUND: Skin aging is the most common dermatological problem caused by intrinsic and extrinsic factor, such as exposure to (ultraviolet) UV rays. Chlorogenic acid (CA) is a phenolic compound which is known for its antioxidant properties against oxidative stress. OBJECTIVE: This study investigates the antiaging and anti-inflammatory properties of CA on UV-induced skin fibroblast cells. METHODS: Anti-inflammatory properties of CA were assessed by measuring inflammatory-related proteins IL-1ß and TNF-α, while antiaging properties of CA were assessed by measuring reactive oxygen species (ROS), apoptosis, live and necrotic cells, and COL-3 gene expression level. RESULTS: Treating UV-induced skin fibroblast cells with CA decreased the level of ROS, IL-1ß, TNF-α, apoptotic cells, and necrotic cells and increased live cells and COL-3 gene expression. CONCLUSION: CA has the potential as the protective compound against inflammation and aging by decreasing the level ROS, pro-inflammatory cytokines IL-1ß and TNF-α, apoptotic cells, and necrotic cells and by increasing live cells and COL-3 gene expression.

Conditioned medium of IGF1-induced synovial membrane mesenchymal stem cells increases chondrogenic and chondroprotective markers in chondrocyte inflammation.

Recently, mesenchymal stem cells (MSCs) have been the most explored cells for cell therapy for osteoarthritis (OA) that can be obtained from various sources. Synovial membrane MSCs (SMMSCs) provide best potential for OA therapy, however they are not widely explored. Conditioned medium of SMMSCs (SMMSCs-CM) rich in growth factors and cytokines can inhibit apoptosis and increase chondrocytes cell proliferation. The aim of the present study was to determine growth factors content in SMMSCs-CM as well as the chondrogenic and chondroprotective markers expression in OA model after insulin-like growth factor (IGF)1-induced and non-induced SMMSCs-CM treatments. Chondrocyte cell line (CHON002) was induced by IL1ß as OA model (CHON002 with IL1ß (IL1ß-CHON002)) and treated with SMMSCs-CM with or without IGF1 induction to determine its effectiveness in repairing OA cells model. ELISA was used to assay BMP2, fibroblast growth factor 18 (FGF18) and transforming growth factor (TGF) ß1 (TGFß1) levels in SMMSCs-CM, matrix metalloproteinase (MMP) 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4) levels in OA cells model treated with SMMSCs-CM. RT-qPCR analyses were used to investigate the gene expression of SOX9, COL2, and COL10. CM from SMMSCs cultured and induced by IGF1 150 ng/mL was the most effective concentration for increasing the content of growth factor markers of SMMSCs-CM, which had successfully increased negative cartilage hypertrophy markers (SOX9 and COL2) and reduced hypertrophy markers (COL10, MMP13, and ADAMTS4). Preconditioning with IGF1 has better and very significant results in lowering MMP13 and ADAMTS4 levels. The present study supports IGF1 pre-conditioned SMMSCs-CM to develop a new therapeutic approach in OA improvement through its chondrogenic and chondroprotective roles.

Anti-allergic Inflammatory Components from the Leaves of Piper crocatum Ruiz & Pav.

Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and ß-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased ß-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.

Hepatotoxicity prevention in Acetaminophen-induced HepG2 cells by red betel (Piper crocatum Ruiz and Pav) extract from Indonesia via antioxidant, anti-inflammatory, and anti-necrotic.

Acetaminophen (APAP) is a widely used analgesic, but it may cause liver injury (hepatotoxicity) via oxidative stress that induced by N-acetyl-p-benzoquinone imine (NAPQI) in long term usage or overdose. Multiple inflammatory mediators were also found to contribute for this effect. Many medicinal plants was known for its antioxidant and anti-inflammatory activities and one of them is Red betel (Piper crocatum Ruiz and Pav) from Indonesia. In this study, the red betel leaves extract (RBLE) protective effect against APAP-induced HepG2 cells was determined. APAP-induced HepG2 as hepatotoxicity cell model was treated with RBLE at 25 and 100 µg/mL. Protective effects of RBLE toward hepatotoxicity were evaluated by several parameters: tumor necrosis factor-α (TNF-α) concentration, reactive oxygen species (ROS) level, live cells percentage, apoptotic cells percentage, necrotic cells percentage, death cells percentage, CYP2E1 and GPX gene expression. The RBLE treatments (both 25 and 100 µg/mL) increased CYP2E1 and GPX gene expression also live cells percentage, while decreased ROS level, TNF-α concentration, also the percentage of death and necrotic cells. Red Betel leaves ethanol extract has hepatoprotective effect via anti-inflammatory, anti-necrotic, and antioxidant potency in liver injury model.

Corilagin potential in inhibiting oxidative and inflammatory stress in LPS-induced murine macrophage cell lines (RAW 264.7).

Objectives: Inflammation is thought to be the common pathophysiological basis for several disorders. Corilagin is one of the major active compounds which showed broad-spectrum biological and therapeutic activities, such as antitumor, hepatoprotective, anti-oxidant, and anti-inflammatory. This study aimed to evaluate the anti-oxidant and anti-inflammatory activities of corilagin in LPS-induced RAW264.7 cells. Materials and Methods: Anti-oxidant activities were examined by free radical scavenging of H2O2, NO, and *OH. The safe concentrations of corilagin on RAW264.7 were determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay on RAW264.7 cell lines. The inflammation cells model was induced with LPS. The anti-inflammatory activities measured IL-6, TNF-α, NO, IL-1ß, PGE-2, iNOS, and COX-2 levels using ELISA assay. Results: The results showed that corilagin had a significant inhibition activity dose-dependently in scavenging activities toward H2O2, *OH, and NO with IC50 values 76.85 µg/ml, 26.68 µg/ml, and 66.64 µg/ml, respectively. The anti-inflammatory activity of corilagin also showed a significant decrease toward IL-6, TNF-α, NO, IL-1ß, PGE-2, iNOS, and COX-2 levels at the highest concentration (75 µM) compared with others concentration (50 and 25 µM) with the highest inhibition activities being 48.09%, 42.37%, 65.69%, 26.47%, 46.88%, 56.22%, 59.99%, respectively (P<0.05). Conclusion: Corilagin has potential as anti-oxidant and anti-inflammatory in LPS-induced RAW 264.7 cell lines by its ability to scavenge free radical NO, *OH, and H2O2 and also suppress the production of proinflammatory mediators including COX-2, IL-6, IL-1ß, and TNF-α in RAW 264.7 murine macrophage cell lines.

Anti-aging Effects of Mangosteen Peel Extract and Its Phytochemical Compounds: Antioxidant Activity, Enzyme Inhibition and Molecular Docking Simulation.

Skin aging is a complex natural process characterised by gradual diminishment of structural integrity and physiological imbalance of the skin tissue. Since the oxidative stress is tightly corelated to the skin aging process, the usage of antioxidant may serve as favourable strategies for slowing down the skin aging process. Mangosteen is an important fruit commodity and its extract had been extensively studied and revealing various biological activities. Present study aimed to assess the antioxidant and antiaging activity of mangosteen peel extract (MPE) and its phytochemical compounds. MPE and its compounds were subjected to ferric reducing antioxidant power (FRAP), hydroperoxide (H2O2) scavenging, anti-collagenase, anti-elastase, anti-hyaluronidase and anti-tyrosinase assay. MPE has the highest FRAP 116.31 ± 0.60 µM Fe(II) µg-1 extract, IC50 of MPE on H2O2 scavenging activity was 54.61 µg mL-1. MPE also has the highest anti elastase activity at IC50 7.40 µg mL-1. Alpha-mangostin showed potent anti-collagenase activity (IC50 9.75 µg mL-1). While gamma-mangostin showed potent anti-hyaluronidase (IC50 23.85 µg mL-1) and anti-tyrosinase (IC50 50.35 µg mL-1). MPE and its compounds were evaluated in vitro for antioxidant and antiaging activities. Current findings may provide scientific evidence for possible usage of mangosteen extract and its compounds as antioxidant and antiaging agent.

Hepatoprotective properties of red betel (Piper crocatum Ruiz and Pav) leaves extract towards H2O2-induced HepG2 cells via anti-inflammatory, antinecrotic, antioxidant potency.

BACKGROUND: Prolonged exposure of free radicals, or known as reactive oxygen species (ROS), in hepatic cells may cause oxidative stress. Without proper treatment, it can induce liver injury and fatal hepatic disease, including cirrhosis. Red betel (Piper crocatum Ruiz and Pav) is one of Indonesia's medicinal plants that has been known to exhibit antioxidant, anti-inflammatory activities. This study aims to determine hepatoprotective effect of red betel leaves extract (RBLE) towards liver injury. METHOD: Hydrogen peroxide-induced HepG2 cells were used as liver injury model·H2O2-induced HepG2 cells were treated with 25 µg/mL and 100 µg/mL RBLE. Several parameters were observed, including TNF-α level through ELISA; necrotic, apoptotic, dead, live cells; and ROS level through flow cytometry analysis; and GPX gene expression through qPCR. RESULT: The study showed that treatment with RBLE were able to decrease TNF-α level; necrotic and death cells percentage; as well as ROS level. On the other hand, it were able to increase apoptotic and live cells percentage; as well as GPX gene expression. Low concentration (25 µg/mL) of RBLE treatment exhibited stronger anti-inflammatory activity as it was resulted in the lower TNF-α level and were able to switched hepatic cell death pathway from necrosis to apoptosis as shown by the shifted of apoptotic cells and necrotic cells percentage. This lead to lower death cells and ultimately improve live cells percentage. Meanwhile high concentration of RBLE (100 µg/mL) exhibited stronger antioxidant properties as indicated by lower ROS level and higher GPX gene expression. CONCLUSION: Overall, this study was able to demonstrate hepatoprotective effect of RBLE towards liver injury model through its anti-inflammatory and antioxidant activities.

Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell.

INTRODUCTION: Breast cancer is one of the leading cause of cancer deaths in women. Metastasis in BC is caused by immunosurveillance deficiency, such NK cell maturation, low NK activity and decreasing cytotoxicity. This study was performed to improve activating receptors and cytotoxicity of NK cells using interleukins (ILs). METHODS: Human recombinant IL-2, -15, and -18 were used to induce NK cells. We measured the activating and inhibiting receptors, proliferation activity of NK cells, and the cytotoxicity of NK cells on BC cells (MCF7). The effects of ILs were tested on the NK cell receptors CD314, CD158a and CD107a with flowcytometry, proliferation at various incubation times with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and concentrations of TNF-α and IFN-γ by NK cells with ELISA. RESULTS: ILs increased NK cell receptor levels (CD314, CD158a, and CD107a) at 24 hours of incubation. ILs increased NK cell viability, which increased with longer incubation. Moreover, ILs-induced NK cells inhibited proliferation in MCF7 cells, as well as increased TNF-α, IFN-γ, PRF1 and GzmB secretion. CONCLUSION: IL-2, IL-15, and IL-18 improved activating receptors and proliferation of NK cells. IL-induced NK cells increased TNF-α, IFN-γ, PRF1 and GzmB secretion and cytotoxic activity on BC cells. High NK cell numbers increased BC cell growth inhibition.

Hypoglycemic Activity of Curcuma mangga Val. Extract via Modulation of GLUT4 and PPAR-γ mRNA Expression in 3T3-L1 Adipocytes.

BACKGROUND: There would be over 600 million people living with diabetes by 2040 as predicted by the World Health Organization. Diabetes is characterized by raised blood sugar and insulin resistance. Insulin regulates the influx of glucose into the cell by upregulating the glucose transporter type 4 (GLUT4) expression on the plasma membrane. Besides, PPAR-γ also controls the metabolism of glucose in adipose tissues. Curcuma mangga Val., denoted as C. mangga, is a native Indonesian medicinal plant that has many beneficial effects, including an antidiabetic potential. PURPOSE: In this research, we aimed to disclose the hypoglycemic activity of ethanol extract of C. mangga (EECM) in 3T3-L1 fibroblasts-derived adipocyte cells in regulating glucose uptake as confirmed by the GLUT4 and PPAR-γ gene expression. METHODS: The uptake of glucose was determined using radioactive glucose, while the gene expression of GLUT4, PPAR-γ, and ß-actin was quantified using mRNA segregation and real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). RESULTS: We discovered that EECM interventions (200 and 50 µg/mL) increased glucose uptake in lipid-laden 3T3-L1 cells by 14.75 and 8.86 fold compared to the control non-insulin, respectively (p < 0.05). At the same doses, they also increased GLUT4 mRNA expression by 8.41 and 11.18 fold compared to the control non-insulin, respectively (p < 0.05). In contrast, EECM interventions (200 and 50 µg/mL) showed lower levels of PPAR-γ mRNA expression compared to the control metformin, indicating the anti-adipogenic potentials of EECM. CONCLUSION: EECM showed hypoglycemic activity in lipid-laden 3T3-L1 cells by improving glucose ingestion into the cells, which was mediated by increased GLUT4 expression and downregulated PPAR-γ expression.