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Aim To observe the effect of betulinic acid (BA) on the migration and invasion of human gastric cancer MKN-45 cells induced by transforming growth factor-pi (TGF-β1), and to explore the effect of BA on epithelial-mesenchymal transition (EMT) and the potential mechanism. Methods The MKN-45 cells were cultivated in vitro, and the effects of different concentrations of BA on the proliferation of MKN-45 cells at 24, 48 and 72 h were detected using CCK-8 method. The effects of BA (5, 10, 20 jjunol • L) and TGF-01 inhibitor LY2109761 (10
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Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.
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Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.
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Target identification of bioactive compounds is important for understanding their mechanisms of action and provides critical insights into their therapeutic utility. While it remains a challenge, unbiased chemoproteomics strategy using clickable photoaffinity probes is a useful and validated approach for target identification. One major limitation of this approach is the efficient synthesis of appropriately substituted clickable photoaffinity probes. Herein, we describe an efficient and consistent method to prepare such probes. We further employed this method to prepare a highly stereo-congested probe based on naturally occurring triterpenoid betulinic acid. With this photoaffinity probe, we identified tropomyosin as a novel target for betulinic acid that can account for the unique biological phenotype on cellular cytoskeleton induced by betulinic acid.
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ObjectiveTo investigate the effect of betulinic acid (BA) on apoptosis and autophagy of human colorectal cancer SW620 cells and the regulatory role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodCell viability was detected by methyl thiazolyl tetrazolium (MTT) colorimetry to determine the optimal administration time and dosage for subsequent experiments. Four groups were designed, including blank group and low-, medium-, and high-dose BA groups. Hematoxylin-eosin (HE) staining was conducted for the observation of SW620 cell morphology, and annexin-V/propidium iodide double staining for the determination of apoptosis rate in SW620 cells. Hoechst33258 staining and MDC staining were used for the observation of apoptosis and autophagy, respectively. Western blotting was employed to determine the protein levels of B-cell lymphoma/leukemia-2(Bcl-2)-associated X protein (Bax), aspartate proteolytic enzyme-9 (Caspase-9), activated aspartate proteolytic enzyme-3 (cleaved Caspase-3), microtubule-associated protein 1 light chain 3 (LC3), the mammalian homolog of yeast Atg6 (Beclin-1), p62, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), and phosphorylated mTOR (p-mTOR) in SW620 cells. ResultBA inhibited the activity of SW620, HT29, and HCT116 cells in a concentration- and time-dependent manner. The cells treated with BA for 48 h had lower viability than those treated for 24 h (P<0.05, P<0.01). The half maximal inhibitory concentration (IC50) value of BA at the time point of 48 h was also lower than that at the time point of 24 h (P<0.01), and that for SW620 cells was the minimum. BA induced the apoptosis in a concentration-dependent manner and increased the autophagosomes. Compared with the blank group, BA increased the apoptosis rate (P<0.01), up-regulated the protein levels of Bax, Caspase-9, cleaved Caspase-3, and LC3 Ⅱ (P<0.05, P<0.01), and down-regulated the protein levels of p62, p-Akt, p-PI3K, and p-mTOR (P<0.01). Additionally, medium- and high-dose BA up-regulated the protein level of beclin-1 (P<0.01). ConclusionBA may inhibit the activity of SW620 cells by hindering the PI3K/Akt/mTOR signaling pathway to induce cell apoptosis and autophagy.
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Aim To survey the effect of betulinic acid against hepatic fibrosis via STAT3 signaling pathway. Methods Raw264. 7 cells were incubated with LPS (1 mg · L
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Betulinic acid (BA) is a lupane pentacyclic triterpene extracted from a variety of Chinese herbs such as Betulae Platyphyllae Cortex, Astragali Radix, Paeoniae Radix Alba, Jujubae Fructus, Sanguisorbae Radix, Eucommiae Cortex, Glycrrhizae Radix et Rhizoma, Aucklandiae Radix, and Ziziphi Spinosae Semen. It has attracted wide attention from doctors because of its low toxicity, high efficacy, and multiple functions. BA has been found to possess a significant anti-tumor biological activity, and it is expected to become a potential drug for the treatment of malignant tumors. So far, a number of studies have shown that BA is able to promote apoptosis, inhibit proliferation, metastasis and invasion, and induce cell cycle arrest via multiple mechanisms, thus resisting various malignant tumors such as ovarian cancer, breast cancer, gastric cancer, lung cancer, colorectal cancer, and prostate cancer. It exerts the anti-tomor effect by regulating the expression of cancer suppressor genes p53 and p21, triggering the generatoipn of reactive oxygen species (ROS), down-regulating the expression of nuclear transcription factor-κB (NF-κB), adjusting the B lymphocytoma-2 (Bcl-2) family to cause tumor cell apoptosis, and regulating transcription factor Sp1/3/4 to induce apoptosis. Its anti-proliferative activity is mainly achieved via the regulation of cyclin B, cyclin D and cyclin dependent kinases CDK and CDC. Its efficacy in inhibiting metastasis and invasion is mainly realized by regulating matrix metalloproteinase (MMP) and matrix metalloproteinase inhibitor (TIMP), up-regulating E-cadherin, down-regulating N-cadherin and blocking the epithelial-mesenchymal transformation (EMT). In addition, BA also induces cell cycle arrest, affects tumor metabolic reprogramming, and activates autophagy to inhibit tumor. Although there are a large number of studies on BA against tumors and its efficacy has been proved strong, the systematic review on its anti-tumor effect is still lacking. Therefore, this study reviewed the anti-tumor effect and mechanism of BA, in order to provide reference for its subsenquent research.
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Natural products are one of the important sources for the discovery of new drugs. Betulinic acid (BA), a pentacyclic triterpenoid widely distributed in the plant kingdom, exhibits powerful biological effects, including antitumor activity against various types of cancer cells. A considerable number of BA derivatives have been designed and prepared to remove their disadvantages, such as poor water solubility and low bioavailability. This review summarizes the current studies of the structural diversity of antitumor BA derivatives within the last five years, which provides prospects for further research on the structural modification of betulinic acid.
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Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.
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Betulinic acid is a natural pentacyclic pentane triterpenoid, usually isolated from the bark of Betula platyphylla, or in the form of free glycosides and glycosyl derivatives in various plants. A variety of derivatives can be obtained by modifying its chemical structure. Betulinic acid and its derivatives have certain regulatory effects in anti-tumor, antiviral, anti-inflammatory, analgesic, inhibition of cerebral nerve and vascular injury, and treatment of other common diseases. The category, pharmacological activities and related mechanisms of betulinic acid and its derivatives are reviewed in this paper, in order to provide a theoretical reference for the future application.
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Objective: To study the chemical constituents of aerial part of Gendarussa vulgaris. Methods: The compounds were separated and purified by silica gel column chromatography, ODS and Sephadex LH-20 chromatography and semi-preparative HPLC. Base on HR-ESI-MS, NMR, and other spectral data, their structures were identified. Results: A total of 17 compounds were isolated from the EtOAc fraction of 95% ethanol extract and identified as 24-norchol-5-en-3β-ol (1), dihydrobetulic acid (2), betulinic acid (3), 3-hydroxy-30-nor-20-oxo-28-lupanoic acid (4), 6-hydroxy-7,8-dimethoxycoumarin (5), 6,7-dimethoxycoumarin (6), 5,6,7- trimethoxycoumarin (7), 6,7,8-trimethoxycoumarin (8), syringaresinol-4-O-β-D-glucopyranoside (9), 4-O-caffeoylquinic acid methyl ester (10), N-trans-feruloyl tyramine (11), N-(2-hydroxy-3-phenylpropyl) acetamide (12), 3-O-caffeoylquinic acid methyl ester (13), 3,5-O-dicaffeoylquinic acid methyl ester (14), p-E-coumarin quinic acid methyl ester (15), 3,4,5-O-tricaffeoyl quinic acid methyl ester (16) and 1'S*,4'R*-8-(4'-hydroxy-2',6',6'-trimethylcyclohex-2-enyl)-6-methyloct-3E,5E,7E-trien-2-one (17). Conclusion: Compounds 1 and 2 are new natural products. All Compounds are isolated from this plant for the first time except compound 6. Besides, all compounds are screened for anti-inflammatory activity and compounds 2, 3, 11, 13, and 17 have NO release inhibiting activities on LPS-induced RAW 264.7 macrophage cells with IC50 values of (30.91 ± 0.50), (44.66 ± 0.56), (17.67 ± 0.57), (28.45 ± 0.67) and (20.79 ± 0.24) μmol/L, respectively.
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Objective: Alysicarpus monilifer (Family Papilionaceae) has been used in the Indigenous system of medicine in tumor removal. The present study was designed to isolate and identify the constituent responsible for cytotoxic (anti-tumor) effects of the plant Alysicarpus monilifer. Methods: The plant was powdered and extracted to give a methanolic extract. Initially, Hexane, chloroform, ethyl acetate and methanolic fractions of the methanolic extract of the plant were subjected to cytotoxic screening using cell line based assay (MTT assay and NRU assay). The chloroform fraction showed significant cytotoxicity, so it was further subjected to column chromatography, to separate the cytotoxic phytoconstituent. The cell lines selected were breast cancer cells (MCF-7 and MDA-MB-468) and Liver cancer cells (HepG2 and HLE cell). Results were calculated as percentage growth inhibition with respect to untreated (control) cells versus treated cells. Result: A triterpene, Betulinic acid, was isolated from the aerial parts of Alysicarpus monilifer. The cytotoxic activity of the identified compound against MCF-7, MDA-MB-231, HLE and HepG2 cells was also found to be highly significant with 90% growth inhibition. Conclusion: The triterpene was identified to be betulinic acid, to which the cytotoxic activity can be attributed. It is a first report of isolation of betulinic acid from the Alysicarpus species.
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Modern extraction technique was investigated for the separation of betulinic acid from the bark of Dillenia indicaLinn. Betulinic acid, a pentacyclic triterpenoid, is a potent anticancer compound and possesses other pharmacologicalactions. The objective of the present study was to investigate the optimum extraction conditions for betulinic acidusing microwave-assisted extraction by applying response surface methodology based on three factors three levelsBox–Behnken experimental design. The extraction was performed by considering three different independent variables:extraction temperature (70°C–90°C), microwave power (100 W), and extraction time (10–20 minutes) and quantifiedusing developed High-performance thin layer chromatography method. The maximum yield of betulinic acid at optimizedexperimental conditions, i.e., 90°C, 200 W, 15 minutes was found to be 0.91%w/w. Analysis of variance showed that the“p-value” was 0.0004 which indicate that the models were statistically significant (p ˂ 0.05). The value of the “coefficientof determination” (R2) for microwave-assisted extraction was 0.94 which indicate that the model shows the goodness offit. To conclude, Microwave Extraction technique along with response surface design proved to be efficient compared toconventional methods which could be applied to isolate active constituents from plant sources.
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Trichomonas vaginalis and Leishmania spp. are protozoal species responsible for millions of cases of parasitic diseases worldwide. Considering the potential of natural products and the need for more effective and less toxic alternatives to treat trichomoniasis and leishmaniasis, this study aimed to evaluate the effect of two series of triterpenes derivatives with different modifications at C-3 and C-28 positions of the ursolic acid (UA) and betulinic acid (BA) against trophozoites of Trichomonas vaginalis and promastigotes forms of Leishmania (L.) amazonensis. The compounds modified just at C-3 were the most active. The 3β-acetyl betulinic acid (1b) reduced the trophozoites viability of T. vaginalis at 74%, followed by the 3-oxo ursolic acid and 3-oxo betulinic acid (3a and 3b) compounds (55% of reduction). The compound 3β-isobutyl ursolic acid (7a) inhibited the viability of L. amazonensis promastigotes by 55%. Therefore, analyzing the structure-activity relationship and the data of literature, it is possible to suppose that the inclusion of polar groups in the skeletons could improve the antiprotozoal activity. Overall, further studies are necessary to develop triterpenic derivatives with more powerful trichomonicidal and leishmanicidal properties.
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Objective: To study the chemical constituents of the stems of Gordonia chrysandra. Methods: The chemical constituents were isolated and purified by column chromatography on silica gel, MPLC and PHPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. Results: Five compounds were isolated from the stems of G. chrysandra and elucidated as 3,4-dimethoxyphenol 1-O-β-D-[6-O-(4-hydroxy-3,5-dimethoxylbenzoate)-glucopyranoside (1), 3,4,5- trimethoxyphenyl-6- O-vanilloyl-β-D-glucoside (2), 2α,3β,19α-trihydroxyolean-12-en-23,28-dioic acid (3), betulinic acid (4), 3-O-β-D-galactopyranosyl- (1→2)-[β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl-(1→3)]-β-D-glucuronopyranosyl-3β,16α,22α,28-tetrahydroxy-22-O-tigloyloxy- olean-12-ene-23-al (5). Conclusion: Compound 1 is a new compound named chrysandroside A, and compounds 3-5 are isolated from this plant for the first time.
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Objective: To study the chemical constituents of Hypericum monogynum. Methods: The chemical constituents were isolated and purified by solvent extraction method, the normal and reverse phase silica gel column chromatography and semi-preparative high performance liquid chromatography. Results: Six compounds were isolated from the chloroform extract of H. monogynum. Their structures were identified as hypermongone A (1), β-sitosterol (2), 5α,8α-epidioxyergosta-6,22-dien-3β-ol (3), isocudraniaxanthone B (4), betulinic acid (5), and 2-hydroxydiplopterol (6) by the physicochemical properties and modern spectroscopic methods. Conclusion: Compound 1 is a new compound, and compounds 3, 4, and 6 are isolated from H. monogynum for the first time.
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Objective: To prepare compounded nanosuspensions of paclitaxel and betulinic acid nanosuspension and optimize the preparation process. Methods: Nanosuspension was prepared by high pressure homogenization with poloxamer 188 and lecithin as stabilizer. Stabilizer concentration, stabilizer ratio, homogeneous pressure, and cycle times were selected as investigation factors and the particle size and PDI of nanosuspension were selected as evaluation index to optimize the prescription by Box-Behnken design-response surface method and the in vitro evaluation was determined. Results: The optimal formulation was as follows: stabilizer concentration 0.6 mg/mL, poloxamer 188-lecithin (2∶1), homogenous pressure 100 MPa, cycle times 20 times. The average particle size was (282.54 ± 5.40) nm, PDI was 0.242 ± 0.020. The nano-particles in the paclitaxel-betulinic acid compounded nanosuspension were rod-shaped. The nanosuspension had perfect redispersibility and satisfactory short-term stability. Paclitaxel and betulinic acid in nano lyophilized powders all existed in amorphous form. After being prepared into nanosuspension formulation, the solubility of paclitaxel in water was increased by about 90 times while that of betulinic acid was increased by about 100 times. In 2 h, the cumulative dissolution rate of paclitaxel and betulinic acid in nanosuspension of paclitaxel and betulinic acid were all up to 95%. Conclusion: Optimizing the preparation process of nano-suspension with Box-Behnken design-response surface method is effective and feasible and nanosuspension formulation can improve the dissolution of paclitaxel and betulinic acid observably.
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@# Objective: To investigate the effects and the underlying mechanisms of betulinic acid (BEA) on sensitizing pancreatic cancer cell lines Panc-1 and Miapaca-2 to gefitinib. Methods: After the cell culture was completed, Panc-1 and Miapaca-2 cells were randomly divided into 4 groups: control group (without treatment), BEAgroup, gefitinib group and BEAcombined with gefitinib group, respectively.The sensitization effect of BEAon gefitinib-insensitive pancreatic cancer cells was detected by MTS assay. The treatment effects of combined treatment of gefitinib and BEA against Panc-1 and Miapaca-2 cells were evaluated by colony formation assay. Flow cytometry was used to examine the effect of BEAon apoptosis of Panc-1 cells while WB was applied to determine the effect of BEAonapoptosis-related proteins. Surface plasmon resonance (SPR) experiment was used to detect the direct combination between signal transducer and activator of transcription 3(STAT3) and BEA; Molecular docking and molecular dynamics simulation experiments were adopted topredict the combining mode between STAT3 and BEA. Results: BEA synergistically enhanced the gefitinib-sensitivity of pancreatic cancer Panc-1 and Miapaca-2 cells (P<0.05), and IC50 of gefitinib on two cells were reduced by over 50%. Compared with single treatment, the combined treatment of BEA and gefitinib promoted the apoptosis and up-regulated the expressions of apoptosis-relatedproteins (cleaved-PARP and Bax), but reduced the apoptosis-inhibitory protein Bcl-2 (all P<0.05 or P<0.01). Moreover, the inhibitory effect of BEA on STAT3 activation in Panc-1 cells was in a dose-dependent mannar (P<0.01). BEA stabilizes its binding to STAT3 by forming hydrogen bonds with Lys-591 and Ser-613 of STAT3; in the meanwhile, BEA stabilized inthebinding site of STAT3, there by blocking STAT3 dimerization to enhance the drug sensitivity. Conclusion: Combined use of BEA and gefitinib could significantly inhibit the proliferation and induce apoptosis of Panc-1 and Miapaca-2 cells, which might be mediated by the inhibition of BEA on STST3.
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Objective To investigate the effects of betulinic acid on spatial learning and memory in rats with type 2 diabetes mellitus(T2DM) and to explore its underlying mechanisms.Methods Forty-five male Wistar rats were randomly divided into control group (Sham),T2DM group and betulinic acid treatment group (BA) with 15 in each group.The rats in the latter two groups were given a high fat diet plus low dose of streptozotocin (STZ) to induce T2DM,and the rats in BA group was given 10 mg/kg BA for intragastric administration once daily for 12 weeks,the rats in T2DM group and Sham group were given an equal volume of physiological saline.Morris water maze method was used to detect the cognitive function.The mRNA levels of synaptic plasticity related protein GAP-43,SYP and PSD-95 were detected by RT-PCR.The protein expressions of cholinergic neurotransmitter ChAT and Ach were detected by Elisa.Results Compared with the Sham group,the escape latency of the T2DM group was significantly prolonged on days 2-4 ((62.28 ± 2.97)s vs (47.09±2.16)s;(48.52±3.09) s vs (26.18±2.21)s;(42.31±2.80)s vs (13.42±1.23)s),the original platform quadrant time was significantly reduced ((24.60±2.42) s vs (41.85 ± 1.98) s),GAP-43,SYP,ChAT and Ach levels were significantly lower,the differences were statistically significant (the t values were 16.37,22.34,39.78,20.42,116.01,91.35,71.84,21.88 and 21.11,respectively,all P< 0.05).Compared with T2DM group,the escape latency of BA group in 2-4 days were significantly shortened ((55.61±2.75)s vs (62.28±2.97)s;(31.35±2.63)s vs (48.52±3.09)s;(42.31±2.80)s vs (16.58± 1.37) s),the original platform quadrant time increased significantly ((37.58± 2.31) s vs (24.60±2.42) s),and GAP-43,SYP,PSD-95,ChAT and Ach levels were significantly higher,and the differences were statistically significant (the t values were 6.80,16.21,33.54,14.55,41.83,35.23,36.20,12.82 and 9.97,respectively,all P<0.05).Conclusion Betulinic acid can improve the spatial learning and memory of type 2 diabetic rats,and increasing the expression of GAP-43,SYP,PSD-95,ChAT and Ach may be its potential mechanism.
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ABSTRACT Diabetes is a metabolic disease caused by abnormal insulin secretion or action. In the present study, the effects of betulinic acid (BA, a triterpene) are evaluated on glucose, α-amylase and plasma insulin levels, insulin resistance and the histopathology of pancreatic islets in streptozotocin-nicotinamide (STZ-NA) diabetic mice. Seventy adult male NMRI mice were randomly divided into seven groups: control, sham, diabetic, diabetic treated with BA (10, 20 and 40 mg/kg) and diabetic treated with metformin (200 mg/kg). Diabetes was induced in mice by intraperitoneal injection of streptozotocin 50 mg/kg after a dose of nicotinamide 120 mg/kg. Two weeks after treatment with BA, blood samples were collected for measuring glucose, α-amylase and insulin levels, and the pancreas was isolated for histopathology evaluation. Diabetes reduced the number and diameter of pancreatic islets, and increased α-amylase and insulin resistance. BA treatment reduced blood glucose, α-amylase and improved insulin sensitivity as well as pancreas histopathology. In addition, BA showed stronger effects on the pancreatic histology and insulin resistance compared to the metformin group