Oleanolic Acid Research Articles

An appraisal of Luffa aegyptiaca extract and its isolated triterpenoidal saponins in Trichinella spiralis murine models

Trichinella spiralis is an intestinal and tissue parasitic nematode, emerging and re-emerging causative agent of a serious foodborne parasitic infection. This study aimed to evaluate the effect of Luffa aegyptiaca leaf extract and its triterpene glycosides on the intestinal and muscle stages of T. spiralis infection in vitro and in vivo . Phytochemical investigations of the extract led to the isolation of five compounds, namely (1) 3- O - β - d -glucopyranosyl-16- O - β -hydroxyolea12-en 23, 28- β - d -diglucopyranoside ester, (2) 3 β -hydroxylolea12-en-28-oic acid (Oleanoic acid), (3) oleanolic acid 3- O - α - l -rhamnopyranosyl-(1 → 4)- β - d -glucopyranoside, (4) 3- O - β - d -glucopyranosyl-28- β - d -glucopyranosyl oleanolate, and (5) stigmast-5, 22-dien-3- O - β - d -glucopyrano-side. Moreover, the in vitro study showed marked degeneration and destruction of adult worms and larval teguments with tested drugs. Also, in the in vivo study, mice were divided into six groups; group I: infected and untreated, group II: received leaf extract as prophylaxis, group III: infected and treated with leaf extract, group IV: treated with compound (4), group V: treated with compound (1), and group VI: treated with albendazole. Furthermore, the treatment efficacy was assessed by the adult and total larval counts, histopathological study of the small intestinal and muscle tissues, and immunohistochemical staining of CD34 in muscles. The results revealed a significant reduction of total adult and larval counts in prophylactic and treated groups compared to the positive control group, with a reduction of total adult count by 63.48% and 74.4% in compound (1) and compound (4) treated groups, respectively. Also, a reduction was detected in larval counts by 36.5%, and 93.6% in compound (1) and compound (4) treated groups during both the muscular and intestinal phases, respectively. Additionally, histopathological examination of the small intestine and muscles showed marked improvement with a reduction in the inflammatory infiltrates in treated groups. CD34 expressions were reduced in treated groups with more reduction in compound (4) treated group. In conclusion, this study implies that L. aegyptiaca leaf extract and its tested triterpene glycosides might be used for anti-trichinellosis treatments.

Protective effect of oleanolic acid on liver injury induced by acute exposure to mercury chloride and its possible mechanism

Protective effect of oleanolic acid on liver injury induced by acute exposure to mercury chloride and its possible mechanism

Enhanced Water Solubility and Anti-Tumor Activity of Oleanolic Acid through Chemical Structure Modification.

Cancer has been a major health problem in the world in the past decades. It is urgent to develop new, effective and safe drugs for the treatment of cancer. There are many pentacyclic triterpenoids with positive anti-tumor activity and safety in nature. Oleanolic acid (OA), as one of the pentacyclic triterpenoids, also has broad biological activities including liver protection, anti-inflammatory, hypoglycemic, antiviral and anti-tumor. Therefore, to investigate its anti-tumor activity and mechanism, many OA derivatives have been developed. Some derivatives are less toxic to normal hepatocytes, which may be due to the strong liver protection ability of OA. However, the poor water solubility of OA is one of the main reasons for the weak anti-tumor activity. It is reported that some OA derivatives could enhance solubility by chemically linking some hydrophilic groups to improve anti-tumor activity. This review not only summarizes the highly water-soluble OA derivatives that can improve anti-tumor activity reported in recent years, but also introduces their possible anti-tumor mechanisms.

NRF2 and FXR dual signaling pathways cooperatively regulate the effects of oleanolic acid on cholestatic liver injury

BackgroundPrevious studies have shown that the anti-cholestatic effect of oleanolic acid (OA) is associated with FXR and NRF2. However, how the two signaling pathways cooperate to regulate the anti-cholestatic effect of OA remains unclear. PurposeThis study aimed to further demonstrate the effect of OA on alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury and the interaction mechanism between NRF2 and FXR signaling pathways in maintaining bile acid homeostasis. MethodsGene knockout animals and cell models, metabolomics analysis, and co-immunoprecipitation were used to investigate the mechanism of OA against cholestatic liver injury. ResultsThe effect of OA against ANIT-induced liver injury in rats was dramatically reduced after Nrf2 gene knockdown. With the silencing of Fxr, the hepatoprotective effect of OA was weakened, but it still effectively alleviated cholestatic liver injury in rats. In L02 cells, OA can up-regulate the levels of NRF2, FXR, BSEP and UGT1A1, and reduce the expression of CYP7A1. Silencing of NRF2 or FXR significantly attenuated the protective effect of OA on ANIT-induced L02 cell injury and its regulation on downstream target genes, and the influence of NRF2 gene silencing on OA appeared to be greater. The NRF2 activator sulforaphane, and the FXR activator GW4064 both remarkably promoted NRF2 binding to P300 and FXR to RXRα, but reduced β-catenin binding to P300 and β-catenin binding to FXR. ConclusionThe effect of OA on cholestatic liver injury is closely related to the simultaneous activation of NRF2 and FXR dual signaling pathways, in which NRF2 signaling pathway plays a more important role. The dual signaling pathways of NRF2 and FXR cooperatively regulate bile acid metabolic homeostasis through the interaction mechanism with β-catenin/P300.

Renoprotective effects of oleanolic acid and its possible mechanisms in rats with diabetic kidney disease

Dyslipidemia and inflammation have great roles in the development of diabetic nephropathy (DN). Oleanolic acid (OA) is a natural triterpenoid that possesses multiple pharmacological properties including anti-oxidation, anti-inflammatory and hypoglycemia. In the present study, the effects of OA on diabetic kidney disease (DKD) and its underlying mechanisms were investigated in DKD rats. Twenty-five of a total thirty-five male Sprague-Dawley (SD) rats were used to establish for Type 2 diabetes mellitus (T2DM) model by high-fat diet combined with streptozotocin (STZ). Then rats were randomly assigned into four group: control group (n = 10), T2DM group (n = 9), OA (50 mg/kg) group (n = 7), OA (100 mg/kg) group (n = 8). Rats were sacrificed at the end of 18 weeks after feeding by intraperitoneal injection of pentobarbital sodium. Body weight (BW), fasting blood glucose (FBG), kidney weight (KW), serum lipid, 24-h urinary microalbumin (UMA), serum creatinine (Scr) and uric acid (UA) were measured. Histopathological changes were observed by PAS staining and electron microscope. The expressions of nephrin, CD68, Collagen-IV, AMPK, p-AMPK, PGC-1α, TLR4, NF-κB and TGF-β1 in kidney were also detected by immunohistochemistry or western blot. OA significantly decreased the levels of FBG, kidney index (KI), serum lipid levels, 24 h UMA, Scr, UA in diabetic rats. Additionally, OA obviously attenuated renal lipid accumulation and renal structure abnormalities in diabetic rats. Furthermore, the expression levels of nephrin, p-AMPK/AMPK, PGC-1α were elevated, while CD68, Collagen-IV, TLR4, NF-κB and TGF-β1 expressions were decreased in renal tissues of OA treated diabetic rats. OA showed dose-independent. OA can alleviate renal injury in diabetic rats through improving lipid metabolism and inflammation via AMPK/PGC-1α and TLR4/NF-κB signaling pathway.

Triterpenoids and ultrasound dual-catalytic nanoreactor ignites long-lived hypertoxic reactive species storm for deep tumor treatment

Inducing redox imbalance in cancer cells aided by external stimuli is a promising strategy to treat cancer. However, maximizing efficacious reactive species content with durable effects in deep tumors remains to be challenging. Here, we report an herbal medicine-based nanoreactor (OH7) self-assembled by oleanolic acid (OA) and two sonosensitizers. OH7 couples two cascade reactions under sonication, including dual-sonosensitizer-participated consecutive reactions for generating long-living peroxyl radical (ROO•) and OA-participated serial reactions for forming highly cytotoxic peroxynitrite (ONOO−). The site-directed reactive species burst exerts excellent cytotoxicity on two-dimensional cancer cell cultures and multicellular tumor spheroids. The high elasticity of OH7 for deep tumor transportation, the enhanced intratumoral convection by ultrasound, and the formation of ONOO− to destroy extracellular matrix jointly facilitate satisfactory penetration depth of sonosensitizers. Of note, the deep penetration and the long-lived hypertoxic reactive species generating ability can realize effective tumor inhibition by systemic administration. This study opens up new insights into the reactive species-related bioactive mechanisms to support green development of biocompatible high-performance sonocatalytic nanoreactor for potential clinical applications.

Microemulsions Enhance the In Vitro Antioxidant Activity of Oleanolic Acid in RAW 264.7 Cells.

Oleanolic acid (OA) is the main triterpenic acid of olive leaves known for numerous pharmacological properties, including antioxidant activity. However, it is poorly soluble in water and consequently with low bioavailability, which limits its pharmacological application. Microemulsions (MEs) are dispersed systems consisting of two immiscible phases that promote rapid solubilization and absorption in the gastrointestinal tract. To improve both solubility and intestinal permeability of this molecule, OA has been formulated in two different microemulsions (ME-1 and ME-2). A solubility screening was carried out to select the ME components, and pseudoternary phase diagrams were constructed to evaluate the region of existence and select the appropriate amount of the constituents. ME-1 was prepared using Capmul PG-8/NF as the oily phase, and Transcutol and Tween 20 (7:3) as surfactants, while ME-2 contained Nigella oil and Isopropil myristate as the oily phase, and Transcutol HP and Cremophor EL (2:1) as surfactants. The OA solubility was increased by 1000-fold and 3000-fold in ME-1-OA and ME-2-OA, respectively. The MEs’ droplet size and the PdI were evaluated, and the stability was assessed for 8 weeks by monitoring chemical and physical parameters. The parallel artificial membrane permeability assay (PAMPA) also demonstrated an enhanced intestinal permeability of both OA formulations compared with free OA. The potential ability of both MEs to enhance the bioactivity of OA against LPS-induced oxidative stress in RAW 264.7 murine macrophages was also investigated. Overall, this study suggests that both MEs promote a bio-enhancement of the protective action of OA against the LPS-induced pro-oxidant stress in macrophages. Overall, this study suggests that MEs could be an interesting formulation to improve OA oral bioavailability with potential clinical applications.

Evaluation of the Phytochemical Composition of Phenolic and Triterpene Compounds in Fruit of Large Cranberries (Vaccinium macrocarpon Aiton) Grown in Latvia.

We carried out a qualitative and quantitative analysis of the phytochemical composition of the fruits of large cranberry cultivars ‘Ben Lear’, ‘Bergman’, ‘Kalnciema agra’, ‘Lemunyon’, ‘Pilgrim’, ‘Stevens’, and ‘Tina’ grown in Latvian climatic conditions. The following predominant compounds were found in cranberry fruit samples: peonidin-3-O-galactoside, peonidin-3-O-arabinoside, cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, myricetin-3-galactoside, quercetin-3-galactoside, quercetin-3-α-L-arabinofuranoside, quercetin 3-rhamnoside, ursolic acid, and oleanolic acid. During the berry ripening period (from 16 August until 15 September), a trend of decreasing amounts of compounds was found in the fruit samples of the studied cranberry cultivars: the total amount of proanthocyanidins decreased by 1.3 times, the total amount of the identified flavonols decreased by 1.3 times, the total amount of triterpenoids decreased by 1.2 times, and the total amount of chlorogenic acid decreased by 1.7 times. During the period from 16 August until 15 September, the total amount of anthocyanins in the cranberry fruit samples increased by 2.6 to 17 times. The highest total amount of anthocyanins (5305.80 ± 27 µg/g) was detected in fruit samples of the cranberry cultivar ‘Kalnciema agra’ collected on 15 September. The amount of biologically active compounds in cranberry fruit samples varies during berry ripening. Thus, the choice of the picking time is one of the factors that determines the phytochemical composition of raw cranberry material.

Discovery of 12β-oxygenated oleanolic acid alkyl esters as potent and selective FXR modulators exhibiting hyperglycemia amelioration in vivo

Farnesoid X receptor (FXR) ligands have been actively pursued to treat metabolic disorders, liver and bile diseases, among others. Starting from a widely occurring natural product, oleanolic acid (OA), we discovered potent and selective FXR modulator from the 12β-oxygenated OA alkyl esters, with the assistance of molecular modeling. The representative compound 7b modulated some FXR downstream genes involved in glucose and lipid metabolism in cells, and significantly improved hyperglycemia in KKay fat mice fed with high fat diet, through the reduction of mRNA expression of gluconeogenesis genes PEPCK and G6Pase. This study provides a new series of selective FXR modulator, as well as the in vitro and in vivo evidence for their potential to improve hyperglycemia in diabetic mice through FXR antagonism.

MEASUREMENT UNCERTAINTY EVALUATION OF ANALYTICAL METHOD FOR QUANTITATIVE DETERMINATION OF URSOLIC AND OLEANOLIC ACIDS IN APPLE PROCESSING AGROINDUSTRIAL WASTE MATERIAL

Background: Apple pomace represents a low-cost and rich source of bioactive compounds with valuable properties - ursolic acid (UA) and oleanolic acid (OA). Due to the wide range of applications in pharmaceutical and nutraceutical industries, these compounds have a high commercial value, and possessing a suitable analytical method with measurement uncertainty is of great significance and practicability. Aim: The purpose of the present work was to estimate detailed measurement uncertainty for the validated HPLC method combined with the extraction procedure for the determination of UA and OA in apple pomace. Methods: The chromatographic analysis using LC-20AD Prominence Shimadzu System and ultrasound-assisted extraction using the ultrasonic bath DW-5200DTS were performed to obtain and determine UA and OA in apple pomace. The process of measurement uncertainty evaluation was performed by the Ishikawa diagram and a combination of bottom-up and top-down approaches. Results: The content of UA and OA (mg/g) in apple pomace with the value of the expanded uncertainty was calculated, which is 7.06 ± 0.647 mg/g (k=1.96; P=95%) and 4.70 ± 0.422 mg/g (k=1.96; P=95%), respectively. Six sources of all the contributors of uncertainties were observed that affected the measurement. Discussion: The A-type standard uncertainty value was 3 times less than the B-type standard uncertainty for both analytes. The results show that B-type standard uncertainty is a major contributor, and the value of the expanded uncertainty of the validated method will not change from test to test in the same laboratory conditions. Conclusions: The methodology described in this work explains well the details and practical aspects of the hybrid approach using the method validation data and proposes step-by-step instructions to evaluate the measurement uncertainty of the quantitative method.

Biosynthesis Investigations of Terpenoid, Alkaloid, and Flavonoid Antimicrobial Agents Derived from Medicinal Plants.

The overuse of antibiotics in the past decades has led to the emergence of a large number of drug-resistant microorganisms. In recent years, the infection rate caused by multidrug-resistant microorganisms has been increasing, which has become one of the most challenging problems in modern medicine. Plant-derived secondary metabolites and their derivatives have been identified to display significant antimicrobial abilities with good tolerance and less adverse side effects, potentially having different action mechanisms with antibiotics of microbial origin. Thus, these phyto-antimicrobials have a good prospect in the treatment of multidrug-resistant microorganisms. Terpenoids, alkaloids, and flavonoids made up the predominant part of the currently reported phytochemicals with antimicrobial activities. Synthetic biology research around these compounds is one of the hotspot fields in recent years, which not only has illuminated the biosynthesis pathways of these phyto-antimicrobials but has also offered new methods for their production. In this review, we discuss the biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents—using artemisinin and oleanolic acid (terpenoids), berberine and colchicine (alkaloids), and baicalin (flavonoids) as examples—around their antimicrobial action mechanisms, biosynthesis pathway elucidation, key enzyme identification, and heterologous production, in order to provide useful hints for plant-derived antimicrobial agent discovery and development.

Isolation & identification of anti-inflammatory constituents of Randia dumetorum lamk. fruit: Potential beneficial effects against acute lung injury

Ethnopharmacological relevanceRandia dumetorum Lamk. is an Indian traditional medicinal plant that has been used for the treatment of various disorders including respiratory ailments. Aim of the studyIn continuation of our recent report that the Ethanol soluble fraction (ESF) of Randia dumetorum fruit had potent anti-inflammatory activity against acute lung injury (ALI) in mice, the present work was undertaken to unveil the key bioactive constituents possessing anti-inflammatory action against ALI by employing bioactivity-guided fractionation of ESF. Material and methodsDifferent fractions/sub-fractions obtained by column chromatography of ESF were subjected to bioactivity studies by analyzing total and differential count, and protein content in broncho-alveolar lavage fluid (BALF) procured from mice. The most bioactive sub-fraction F3.2 was analyzed for the assessment of various inflammatory mediators using molecular techniques like ELISA, PCR, and western blotting. Further, an attempt was made to separate the key compounds in F3.2 using solvents of differential polarities; and isolated compounds were validated for their anti-inflammatory activity followed by their characterization using spectral techniques like 1HNMR, 13CNMR, FT-IR, and ESIMS Mass Spectrometry. ResultsThe column chromatography of ESF yielded four fractions (F1, F2, F3, and F4) and data revealed that maximum activity resides in F3. Further fractionation of F3 yielded sub-fractions F3.1, F3.2, F3.3, and F3.4 which when tested for anti-inflammatory potential, showed F3.2 as the most active one. Moreover, the effect of F3.2 on oxidative stress parameters and inflammatory mediators analyzed via biochemical assays, PCR, and ELISA revealed the proficiency of this fraction in amelioration of ALI. F3.2 was then subjected to recrystallization using different solvents and two pure compounds were isolated which were characterized as D-Mannitol and Oleanolic acid (OA). D-Mannitol did not display any bioactivity, but OA showed potent anti-inflammatory activity. ConclusionConsidering the ethnopharmacological role of R. dumetorum in respiratory ailments, OA as an aglycone moiety seems to be the main active principle possessing anti-inflammatory potential against ALI.

Pentacyclic triterpenes modulate farnesoid X receptor expression in colonic epithelial cells: Implications for colonic secretory function

The nuclear bile acid receptor, farnesoid X receptor (FXR), is an important regulator of intestinal and metabolic function. Previous studies suggest that pentacyclic triterpenes (PCTs), a class of plant-derived bioactive phytochemical, can modulate FXR activity and may therefore offer therapeutic benefits. Here, we investigated the effects of a prototypical PCT, hederagenin (HG), on FXR expression, activity, and antisecretory actions in colonic epithelial cells. T84 cells and murine enteroid-derived monolayers were employed to assess HG effects on FXR expression and activity in colonic epithelia. We measured mRNA levels by qRT-PCR and protein by ELISA and immunoblotting. Transepithelial Cl- secretion was assessed as changes in short circuit current in Ussing chambers. We determined HG treatment (5-10μM) alone did not induce FXR activation but significantly increased expression of the receptor, both in T84cells and murine enteroid-derived monolayers. This effect was accompanied by enhanced FXR activity, as assessed by FGF-15/19 induction in response to the synthetic, GW4064, or natural FXR agonist, chenodeoxycholic acid. Effects of HG on FXR expression and activity were mimicked by another PCT, oleanolic acid. Furthermore, we found FXR-induced downregulation of cystic fibrosis transmembrane conductance regulator Cl- channels and inhibition of transepithelial Cl- secretion were enhanced in HG-treated cells. These data demonstrate that dietary PCTs have the capacity to modulate FXR expression, activity, and antisecretory actions in colonic epithelial cells. Based on these data, we propose that plants rich in PCTs, or extracts thereof, have excellent potential for development as a new class of "FXR-targeted nutraceuticals".

Antioxidant activity of isolated compounds from ethyl acetate extract of Bruguiera parviflora

Bruguiera parviflora belongs to Bruguiera genus, which possesses several biological activities such as antidiabetic, anti-inflammation, antioxidant. Phytochemical investigation of the ethyl acetate extract from Bruguiera parviflora leaves was carried out bioassay guided isolation and obtained three known compounds, namely kochioside A (1), oleanolic acid (2) and quercitrin (3). The chemical structure of isolated compounds were elucidated by spectroscopic data analysis as well as the comparison of their NMR data with the ones published in the literatures. All isolated compounds were evaluated for antioxidant activity with the free radical scavenging ability on 1,1-diphenyl-2-picrylhydrazyl (DPPH). Among them, quercitrin (3) was the most potent compound against DPPH with the IC50 value of 16.4 ± 0.2 g/mL, compared to vitamin C, which was used as positive control.

Elucidation of active ingredients and mechanism of action of hawthorn in the prevention and treatment of atherosclerosis.

Hawthorn (HT), a functional food and medicinal herb for centuries in China, has potential preventive and therapeutic effects on atherosclerosis (AS). However, the mechanisms and active ingredients of HT in the prevention and treatment of AS are unclear. This study aimed to reveal active components and mechanism of HT in the prevention and treatment of AS using UHPLC-Q-Exactive Orbitrap MS and network pharmacology. A total of 50 compounds were identified by UHPLC-Q-Exactive Orbitrap MS. Six core targets and six active compounds were obtained by network pharmacology. Apigenin, luteolin, chrysin, quercetin, oleanic acid, and corosolic acid were the active components in the prevention and treatment of AS, and core targets included SRC, HSP90AA1, MAPK3, EGFR, HRAS, and AKT1. The key signaling pathways involved are MAPK, HIF-1, NF-kappa B, PI3K-Akt, TNF, Rap1, Ras, and VEGF signaling pathways. Further molecular docking results indicated that the six active compounds had strong hydrogen bonding ability with the six core targets. On the molecular level, HT may regulate AS by controlling cell survival and proliferation, reducing the levels of enzymes HMG-CoA reductase and lipoprotein lipase and inhibiting inflammatory response. PRACTICAL APPLICATIONS: HT can serve as "medicine-food homology" for dietary supplement and exert potential preventive and therapeutic effects on AS. However, the mechanisms of HT in the prevention and treatment of AS are unclear. This study describes a rapid method of detecting and identifying the components and mechanism of HT based on LC-MS and network pharmacology, which provides a theoretical and scientific support for further application of HT and guidance for the research of other herbal medicines.

Ursolic and oleanolic acids in combination therapy inhibit migration of colon cancer cells through down-regulation of the uPA/uPAR-dependent MMPs pathway

BackgroundColorectal cancer is one the most lethal cancers worldwide. Since chemotherapy is burdened with harmful effects, agents capable of enhancing the chemotherapeutic effect are being sought. Ursolic acid (UA) and oleanolic acid (OA) were analyzed for such properties. The aim of the study was to evaluate the ability of UA and OA administered individually and in combination with each other and/or a cytostatic drug camptothecin-11 (CPT-11) to limit the viability and migration of colorectal cancer cells. Materials and methodsThe cytotoxic effect of UA, OA and CPT-11 and impact on normal and cancer cell migration rate were assessed. Furthermore, the effect on factors crucial in cancer metastasis: MMP-2 and -9, uPA/uPAR, and E-cadherin were assessed with ELISA, Western Blotting and immunofluorescence assays. Statistical analysis was performed with One-Way Anova with Dunnett's test. ResultsThe studied compounds exhibited the most favorable properties, i.e. they reduced the viability and migration of cancer cells. Furthermore, the secretion, activity, and cellular level of cancer MMP-2 and -9 were decreased, as a result of uPA/uPAR down-regulation. The agents also increased the level of cellular E-cadherin. The effect of the studied agents on normal cells was milder. ConclusionsThe compounds exhibited stronger activity when administered in combination and, combined with CPT-11, enhanced anti-tumorigenic activity of the drug. The migration-limiting activity was based on down-regulation of the uPA/uPAR-dependent MMP pathway. Moreover, UA and OA exhibited a protective effect towards normal cells.

Modulation of grape cuticular wax composition following multiple heatwaves influences grape transpiration

Heat stress events (heatwaves) significantly impair grapevine leaf and berry physiology. The prevalence and frequency of heatwaves are predicted to increase in the coming decades, even in moderate climates. Despite this, many facets of heatwave effects on grapevine physiology remain unstudied. In this work, we subjected potted Gewürztraminer grapevines to a single heatwave event at mid-ripening or a double heatwave event at both the onset of ripening and mid-ripening and compared them to respective untreated control vines. The recovery of leaf and grape physiology from both events were analyzed on the day following the event and at harvest maturity through measurements of leaf gas exchange and chlorophyll fluorescence, and grape size, total soluble solids, and cuticular wax composition. Both single heatwave (S-HW) and double heatwave ( D -HW) treatments reduced chlorophyll fluorescence ( Fv/Fm ) by 12.8 % and 6.1 % on the day following the heatwave, respectively. However, values recovered at harvest maturity only by S-HW. Photosynthetic rate (Pn) was not affected by treatments on the day following the heatwave, but was reduced in D -HW by 48 % at harvest maturity. Total soluble solids were also decreased only by D -HW at harvest maturity. Following the D -HW, total berry wax (by 11.8 %), as well as the total contents of triterpenoids (by 11.7 %) and aldehydes (by 14.3 %) were increased significantly at harvest maturity. Fruit cuticular transpiration was reduced by D -HW. Interestingly, this decrease in transpiration was correlated with an increase in the ratio between the two most abundant wax compounds, oleanolic acid and ursolic acid, which are both triterpenoids. This data corroborates to suggest that grapevines are resilient to a single but not a double heatwave event. Future work will further explore the effects of heatwave frequency and recovery on additional facets of leaf physiology and grape quality. • Grapevines were exposed to a single or double heatwave event during ripening. • The double heatwave reduced leaf chlorophyll fluorescence and berry soluble solids. • The double heatwave raised total wax and triterpenoid contents in berries at harvest. • The double heatwave increased the ratio of oleanolic to ursolic acid at harvest. • The oleanolic to ursolic acid ratio correlated with lower cuticular transpiration.

In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus

Objective: Diabetes is a disease that occurs due to pancreatic β cells failing to produce enough insulin or the inability to use the produced insulin effectively in the body. According to the data of the IDF diabetes atlas, it has been reported that there are 537 million diabetic patients aged 20-79 worldwide in 2021 and this number is expected to reach 643 million in 2030 and 783 million in 2045. To control diabetes at such a severe level, scientists are trying to find various treatment methods. One of them is natural treatments. In this study, the affinity values of quercetin, gallic acid, oleanolic acid and ursolic acid, which have antidiabetic properties, to diabetes-related renin, cathepsin-d, T-PA, leptin, MASP-2, FABP4 proteins were investigated. Methods: For molecular docking analysis, unwanted residues and chains were deleted from the proteins with UCSF Chimera 1.15 software and prepared for docking by adding polar hydrogen atoms. Next, quercetin, gallic acid, oleanolic acid and ursolic acid used as ligands were brought to minimum energy conformation. Protein and ligands prepared for molecular docking were analyzed with Autodock Tools 1.5.6 software. Molecular docking results were viewed with BIOVIA Discovery Studio and protein plus software. Moreover, pkCSM software was used for ADME analysis. Conclusion: As a result, quercetin was found to be more effective than the other three flavonoids.

Anticancer activity of oleanolic acid and its derivatives modified at A-ring and C-28 position

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Research on the Mechanism of Liuwei Dihuang Decoction for Osteoporosis Based on Systematic Biological Strategies.

Background Osteoporosis is an important health problem worldwide. Liuwei Dihuang Decoction (LDD) and its main ingredients may have a good clinical effect on osteoporosis. Meanwhile, its mechanism for treating osteoporosis needs to be further revealed in order to provide a basis for future drug development. Methods A systematic biological methodology was utilized to construct and analyze the LDD-osteoporosis network. After that, the human transcription data of LDD intervention in patients with osteoporosis and protein arrays data of LDD intervention in osteoporosis rats were collected. The human transcription data analysis, protein arrays data analysis, and molecular docking were performed to validate the findings of the prediction network (LDD-osteoporosis PPI network). Finally, animal experiments were conducted to verify the prediction results of systematic pharmacology. Results (1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and β-catenin mRNA expression (P < 0.05). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1. Conclusion LDD may have a therapeutic effect on osteoporosis through regulating the targets (such as ALB, IGF1, SRC, and ESR1), biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) found in this research.