Maslinic Acid Research Articles

Triterpenes from Olea europaea modulate in vitro ruminal fermentation.

Bioactive compounds present in Olea europaea have shown promising antimicrobial potential as an alternative to conventional coccidiostats. These effects are exerted by triterpenic acids (TT) present in the olive plant, namely, oleanolic acid (OA), ursolic acid (UA), and maslinic acid (MA). The objective of this study was to determine the effects of OA, UA, and MA on in vitro ruminal fermentation in comparison with monensin (MON). The study consisted of two experiments conducted as randomized complete block designs using bahiagrass hay or a high-concentrate mixed ration as basal substrates. In the first experiment (Exp. 1), a batch culture was performed with increasing doses of OA, UA, or MA. In Exp. 2, to increase the solubility of OA, two chemical forms were evaluated: a sodium salt (OA-NA) or a phyto-phospholipid complex (OA-PHYT) at 0, 4, 40, 100, and 200 mg/L of incubation inoculum. In both experiments, the dose 0 was used as control (CTL) and monensin (MON) as a positive control. Data were analyzed as a randomized complete block design with a factorial arrangement of treatments. For Exp. 2, orthogonal polynomial contrasts, adjusted for unequal spacing were used to determine the linear effects of increasing doses of OA-NA and OA-PHYT. In Exp. 1, OA reduced the concentration of CH4 in the high-concentrate substrate compared with CTL (P = 0.04). In Exp. 2 the total gas production was linearly decreased with increasing doses of OA-NA in both substrates (P ≤ 0.02). Furthermore, OA-NA and OA-PHYT decreased in vitro organic matter digestibility (P < 0.01) in the bahiagrass substrate to the same extent that MON did. However, the concentration of CH4/g of incubated DM was only reduced by the highest doses of OA-NA (P < 0.02). Lastly, no effects were observed for total VFA nor the VFA profile; however, OA-NA linearly decreased the A:P ratio in the bahiagrass substrate (P = 0.03). In conclusion, the acid form of OA as well as the sodium salt and phyto-phospholipid complex of OA were able to modify some fermentation parameters in this study; however, the magnitude of the responses was lower compared with monensin. Future studies should test OA in vivo to determine if the effects on ruminal fermentation observed here can translate into improve production efficiency while reducing carbon emissions.

Maslinic acid protects against pressure-overload-induced cardiac hypertrophy by blocking METTL3-mediated m6A methylation.

Coordinated response of the heart to physiological stressors (including stress overload, ischemia, hypothyroidism, and metabolic signals) is a hallmark of heart disease. However, effective treatment and its molecular targets are unknown. Although Maslinic Acid (MA) has been shown to inhibit inflammatory responses with strong anti-tumor, anti-bacterial, and antioxidant effects, information on its role and underlying mechanism in cardiac hypertrophy are scanty. The present study revealed that 10-103 μg/ml MA treatment significantly inhibited Ang-II induced hypertrophy in NMCMs and the dosage did not influence the cell viability of H9C2 and NCMCs. Moreover, the anti-hypertrophy effect of MA (30 mg/kg·day) was verified in the TAC-induced hypertrophy mouse model in vivo. Further analysis showed that MA administration decreased the total RNA m6A methylation and METTL3 levels in Ang-II treated NMCMs and TAC stressed hearts. Rescue experiments under adenovirus-mediated myocardial METTL3 overexpression confirmed that METTL3-mediated m6A methylation is essential in M-driven inhibition of myocardial hypertrophy. Collectively, MA exerts a significant anti-hypertrophy effect by regulating the modification of METTL3-mediated m6A methylation in vitro and in vivo. These findings may provide a platform for establishing a new target and strategy for cardiac hypertrophy treatment.

Engineering of Yarrowia lipolytica for the production of plant triterpenoids: Asiatic, madecassic, and arjunolic acids

Several plant triterpenoids have valuable pharmaceutical properties, but their production and usage is limited since extraction from plants can burden natural resources, and result in low yields and purity. Here, we engineered oleaginous yeast Yarrowia lipolytica to produce three valuable plant triterpenoids (asiatic, madecassic, and arjunolic acids) by fermentation. First, we established the recombinant production of precursors, ursolic and oleanolic acids, by expressing plant enzymes in free or fused versions in a Y. lipolytica strain previously optimized for squalene production. Engineered strains produced up to 11.6 mg/g DCW ursolic acid or 10.2 mg/g DCW oleanolic acid. The biosynthetic pathway from ursolic acid was extended by expressing the Centella asiatica cytochrome P450 monoxygenases CaCYP716C11p, CaCYP714E19p, and CaCYP716E41p, resulting in the production of trace amounts of asiatic acid and 0.12 mg/g DCW madecassic acid. Expressing the same C. asiatica cytochromes P450 in oleanolic acid-producing strain resulted in the production of oleanane triterpenoids. Expression of CaCYP716C11p in the oleanolic acid-producing strain yielded 8.9 mg/g DCW maslinic acid. Further expression of a codon-optimized CaCYP714E19p resulted in 4.4 mg/g DCW arjunolic acid. Lastly, arjunolic acid production was increased to 9.1 mg/g DCW by swapping the N-terminal domain of CaCYP714E19p with the N-terminal domain from a Kalopanax septemlobus cytochrome P450. In summary, we have demonstrated the production of asiatic, madecassic, and arjunolic acids in a microbial cell factory. The strains and fermentation processes need to be further improved before the production of these molecules by fermentation can be industrialized.

Maslinic Acid Protects against Streptozotocin-Induced Diabetic Retinopathy by Activating Nrf2 and Suppressing NF-κB.

This study tested the protective effect of maslinic acid (MA) against diabetic retinopathy (DR) in rats with type 1 diabetes mellitus (T1DM) and investigated possible mechanisms of action. DM was introduced by streptozotocin (STZ) (65 mg/kg, i.p.). Control and STZ (T1DM) were divided into 2 subgroups, which received either the vehicle or MA (80 mg/kg). Serum, pancreases, and retinas were collected for further use. MA significantly reduced fasting glucose levels in the control and T1DM rats but enhanced fasting insulin levels and partially increased the size of the islets of Langerhans and the number of β-cells in T1DM rats. In addition, MA significantly improved the retina structure by preventing the reduction in the area between the inner and outer limiting membranes (ILM and OLM, respectively) and increasing the number of cells forming the ganglion cell layer (GCL), inner nuclear layer (INL), and outer nuclear layer (ONL). Associated with these effects, MA significantly reduced the total levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as the nuclear levels of NF-κB p65, mRNA levels of Bax, and protein levels of cleaved caspase-3 in the retinas of T1DM rats. However, MA significantly lowered levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but significantly increased the nuclear levels of Nrf2, protein levels of Bcl2, and total levels of superoxide dismutase (SOD) and reduced glutathione (GSH) in the retinas of the control and T1DM rats. In conclusion, MA prevents DR by antioxidant potential mediated by the activation of Nrf2.

Identification of Corosolic and Oleanolic Acids as Molecules Antagonizing the Human RORγT Nuclear Receptor Using the Calculated Fingerprints of the Molecular Similarity.

RORγT is a protein product of the RORC gene belonging to the nuclear receptor subfamily of retinoic-acid-receptor-related orphan receptors (RORs). RORγT is preferentially expressed in Th17 lymphocytes and drives their differentiation from naive CD4+ cells and is involved in the regulation of the expression of numerous Th17-specific cytokines, such as IL-17. Because Th17 cells are implicated in the pathology of autoimmune diseases (e.g., psoriasis, inflammatory bowel disease, multiple sclerosis), RORγT, whose activity is regulated by ligands, has been recognized as a drug target in potential therapies against these diseases. The identification of such ligands is time-consuming and usually requires the screening of chemical libraries. Herein, using a Tanimoto similarity search, we found corosolic acid and other pentacyclic tritepenes in the library we previously screened as compounds highly similar to the RORγT inverse agonist ursolic acid. Furthermore, using gene reporter assays and Th17 lymphocytes, we distinguished compounds that exert stronger biological effects (ursolic, corosolic, and oleanolic acid) from those that are ineffective (asiatic and maslinic acids), providing evidence that such combinatorial methodology (in silico and experimental) might help wet screenings to achieve more accurate results, eliminating false negatives.

Synthesis, solubility and antitumor activity of maslinic acid derivatives

Maslinic acid (MA), a pentacyclic triterpenoid obtained from olives that is characterized by its antiproliferative activity in tumor cells, has become a promising molecule that could be modified to improve cancer treatment. In this work we have synthesized in good yields several new MA conjugates, including glycerin, oligo(ethylene glycol), and amino acid derivatives (compounds 3a-f). The synthesis offers the possibility of recovering unreacted MA, and thus the scaling up of the process. For the tyramine-MA conjugate, compound 3f or TMA, the preparation has been optimized to a one-pot reaction. Solubility of conjugates in polar solvents has been measured, showing a marked increase of solubility with respect to MA. Moreover, we selected the tyramidyl maslinic acid conjugate (3f or TMA) to determine antitumor capacity over a wide range of cancer cell lines, including glioblastoma, melanoma, breast, lung, colorectal and pancreatic cancer. Our results clearly demonstrated that TMA induced higher cytotoxicity in all cancer cell types compared to MA. TMA was more effective than MA, especially in breast cancer cells (MCF-7) and melanoma cells (B16–F10) where IC50 reductions of 4.12 and 4.72, respectively, was detected. Interestingly, TMA showed a remarkable antitumor ability against the resistant HCT-15 colon cancer cell line. Furthermore, we demonstrated for the first time a relevant effect of a MA derivative against glioblastoma cells (A172 and SF-268). These results suggest that TMA is able to improve the antitumor characteristics of MA in a wide range of cancers and that it may be a promising compound for various tumor types, including resistant cancer.

Maslinic Acid Inhibits Cervical Intraepithelial Neoplasia by Suppressing Interleukin- 6 and Enhancing Apoptosis in a Mouse Model.

Cervical Intraepithelial Neoplasia (CIN) directly precedes cervical cancer, and elevated proinflammatory cytokine Interleukins (IL)-6 is implicated in CIN. As maslinic acid exhibits anti-IL-6 property, the present study sought to determine the effect of maslinic acid on CIN in vitro and in vivo using cell cultures and mouse CIN models, respectively. The dose-effect of maslinic acid on HeLa cells, a human cervical cancer cell line, was first evaluated, including cytotoxicity, IL-6 secretion, IL-6 receptor (IL-6R) expression, proliferation potential and apoptosis status. A mouse model of CIN was also established, which was then subjected to increasing doses of maslinic acid treatment, followed by assessment of serum IL-6 level, cervical expression of IL-6R, and the proliferation potential and apoptosis of cervical tissues. Maslinic acid dose-dependently inhibited cell growth and proliferation potential, reduced IL-6 secretion, cervical expression of IL-6R and induced apoptosis of HeLa cells in vitro. In the CIN mouse model, serum IL-6 level and cervical expression of IL-6R were elevated, which could be repressed by maslinic acid administration dosedependently. Additionally, maslinic acid treatment in the CIN mice could also restore the otherwise increased proliferation potential and reduced apoptosis in the cervical tissues. Maslinic acid exhibits potent anti-IL-6 property in the CIN mouse model, and alleviates the diseaserelated abnormality in proliferation potential and apoptosis state of the cervical tissue cells, demonstrating its usefulness as a promising agent in treating CIN.

Isolation of phytochemicals from Dolichandrone atrovirens followed by semisynthetic modification of ixoside via azomethine ylide cycloaddition; computational approach towards chemo-selection

Aims of the study were the phytochemical investigation and chemical transformation of isolated compounds of medicinal plant listed in ‘Ayurveda’ like Dolichandrone atrovirens, endemic to Indian subcontinents. From chloroform extract of D. atrovirens four compounds; Ursolic acid (1), Maslinic acid (2), Lupeol (3), β-sitosterol (4) and from methanol extract five compounds; β-sitosterol-3-O-β-D-glucopyranoside (5), 10-O-trans-p-Methoxycinnamoylcatalpol (6), Kaempferol-3-O-β-D-glucopyranoside (7), 6-O-[6"(S)-hydroxy-2",6"dimethyl-2"(E)-7"-octadienoyl] catalpol (8) and Ixoside (9) were isolated. Ixoside was used for the semi-synthetic modification via azomethine ylide cycloaddition leading to novel spiro-oxindolo-pyrrolizidine adduct. The structures of novel adducts were elucidated by analysis of IR, MS and 1 D/2D NMR data. Furthermore, to confirm the chemo selection of only one double bond, we performed density functional theory (DFT) calculation, which confirms the chemo selectivity. In addition, in-silico ADME studies and atom-additive approach based on SASA was also examined for the molecules which suggest that they may be potential future candidates for drug discovery.

Isolation of Bioactive Pentacyclic Triterpenoid Acids from Olive Tree Leaves with Flash Chromatography

The present study reports on the use of the flash chromatography for the isolation and purification of oleanolic and maslinic acids from olive leaf extracts. Although the separation and identification of these acids is considered challenging due to the similarity in their structure, oleanolic and maslinic acids were detected, identified, and separated. Solubility prediction was used to help to match compatibility of extraction solvent with targeted triterpenoid acids. Aqueous washing was used, to first selectively remove unwanted interferents from the extraction solvent. The extracts obtained with different solvents and solvent mixtures were fractionated using flash chromatography and then analyzed. HPTLC chromatography was used to assess collected fractions as either semi-pure or pure, and to identify the fractions containing oleanolic and maslinic acids. The yields of oleanolic and maslinic acids reported here are significantly higher than yields obtained in previously reported isolations. The presence and purity of oleanolic and maslinic acid in collected fractions was confirmed by ATR-FTIR and NMR spectrometry.

Maslinic acid activates renal AMPK/SIRT1 signaling pathway and protects against diabetic nephropathy in mice

BackgroundDiabetic nephropathy has been a devastating complication. Clinically, there is an urgent need for nephroprotective agents to delay the onset of diabetic nephropathy and ameliorate its symptoms. Maslinic acid is a pentacyclic triterpene acid with protective effect on multiple organs against oxidative stress and inflammation. In this research, we hypothesized that maslinic acid protects renal function against diabetic nephropathy.MethodsC57BL/6 J male mice administrated with 50 mg/kg of Streptozocin (STZ) daily were used to establish diabetic mouse model (blood glucose levels > 300 mg/dL). Urinary levels of albumin, total proteins, and creatinine were analyzed by an automatic analyzer. H&E staining was used to evaluate renal damage. qRT-PCR and ELISA were performed to investigate the inflammation and oxidative stress in renal tissues. Western blot was used to assess the activation of AMPK signaling.ResultsMaslinic acid treatment alleviated the loss of body weight and blood glucose in diabetic mice. Renal structure and function were protected by maslinic acid in diabetic mice. 20 mg/kg maslinic acid treatment for 8 weeks significantly alleviated the oxidative stress and inflammation in the kidney of diabetic rats. Maslinic acid treatment activated the renal AMPK/SIRT1 signaling pathway.ConclusionMaslinic acid ameliorates diabetic nephropathy and activates the renal AMPK/SIRT1 signaling pathway.

Electrospraying as a Technique for the Controlled Synthesis of Biocompatible PLGA@Ag2S and PLGA@Ag2S@SPION Nanocarriers with Drug Release Capability.

Ag2S nanoparticles are near-infrared (NIR) probes providing emission in a specific spectral range (~1200 nm), and superparamagnetic iron oxide nanoparticles (SPION) are colloidal systems able to respond to an external magnetic field. A disadvantage of Ag2S NPs is the attenuated luminescent properties are reduced in aqueous media and human fluids. Concerning SPION, the main drawback is the generation of undesirable clusters that reduce particle stability. Here, we fabricate biocompatible hybrid nanosystems combining Ag2S NPs and SPION by the electrospraying technique for drug delivery purposes. These nanostructures are composed of poly(lactic-co-glycolic acid) (PLGA) as the polymeric matrix in connection with both Ag2S NPs and SPIONs. Initially, we fabricate a hybrid colloidal nanosystem composed of Ag2S NPs in connection with PLGA (PLGA@Ag2S) by three different routes, showing good photoluminescent (PL) properties with relatively high average decay times. Then, we incorporate SPIONs, obtaining a PLGA polymeric matrix containing both Ag2S NPs and SPION (PLGA@Ag2S@SPION). Interestingly, in this hybrid system, the location of Ag2S NPs and SPIONs depends on the synthesis route performed during electrospraying. After a detailed characterization, we demonstrate the encapsulation and release capabilities, obtaining the kinetic release using a model chemotherapeutic drug (maslinic acid). Finally, we perform in vitro cytotoxicity assays using drug-loaded hybrid systems against several tumor cell lines.

Harnessing the versatility of diverse pentacyclic triterpenoid synthesis through hairy root cultures of various Ocimum species: An unprecedented account with molecular probing and up-scaling access

Biosynthesis of two pharmaceutically and nutraceutically active Pentacyclic-triterpenes (PCTs), namely Corosolic [CA] and Arjunic [AA] acids, had been first time achieved in the hairy root (HR) clones of four Ocimum species (O. basilicum, O. grattisimum, O. kilimandscharicum and O. sanctum), contrasting to their absence in the respective controls. Additionally, compared with each in-vivo controls, their respective HR clones revealed enhanced synthesis of four more PCTs, (i.e., Ursolic acid [UA], Oleanolic acid [OA], Maslinic acid [MA], and Betulinic acid [BA]), in growth dependent manner with notable inter-species yield variations. Real-time analysis revealed noticeable up-regulations of functionally-defined hydroxylase and oxidase genes of CYP716 family in the HR clones over that of their parents, which postulates their possible involvements in the synthesis of CA & AA plus increased levels of the other PCTs in the HR clones. Bioreactor up-scaling further revealed rewarding potentials of the HR technology in Ocimum for synthesis of such distinctive PCTs of immense industrial applications.

Maslinic acid in the treatment of heart damage in obesity hypertension through activating Nrf2 pathway

The present study is to explore the interventional effects and potential mechanisms of Maslinic acid on heart damage in obesity hypertension. The rats were given SHR high-fat diet for 16 weeks. WGA staining and Masson staining were applied to detect heart structure and heart fibrosis degree. WB method was used to detect the expressions of ANP, BNP, P-MHC, TGF-β1, CTGF, Collagen I, Collagen III, Fibronectin and other proteins in SHR heart tissue. ELISA method was used to detect serum TNF-α, IL-6, and PAI-1 content. IF method was employed to detect the expression of Nrf2 in heart tissue. Maslinic acid can significantly improve the morphology of the heart tissue, reduce the hypertrophy and swelling of cardiomyocytes, inhibit the deposition of collagen fibers, and significantly inhibit the expressions of ANP, BNP, MYH7, CTGF, TGFpl, Fibronectin, CollagenI and CollagenIII proteins in the heart tissue. Maslinic acid can effectively inhibit TNF-a, IL-6 and PAI-1 expression, reduce heart inflammation, and significantly elevate Nrf2 level in heart tissue. Maslinic acid can significantly improve the heart structure of obese SHR, inhibit myocardial hypertrophy, cardiac fibrosis, and cardiac inflammation. The underlying mechanism may be related to elevating the expression of Nrf2 protein in the cytoplasm of heart tissue, promoting Nrf2 to enter the nucleus, thereby promoting the expression and activity of mitochondria-function-related proteins. The capabilities to inhibit the expression of hypertrophy-related proteins are also related.

Potential Mechanism of Maslinic Acid against Hypolipidemia Based on Network Pharmacology and Molecular Docking Integration Strategy

Maslinic acid is a pentacyclic triterpenoid acid. Recent research has shown that it has various biological activities such as anti-tumor, hypoglycaemic and hypolipidemic. Among them, the hypolipidemic effect is prominent and this study aims to further explore its mechanism of action in the treatment of hyperlipidemia. The chemical structure of maslinic acid was obtained from PubChem. Based on its chemical structure, the bioavailability and drug-like properties of maslinic acid were analyzed using Swiss absorption, distribution, metabolism and excretion and its potential targets were obtained from SwissTargetPrediction and PharmMapper. Then, the differentially expressed genes between hyperlipidemia patients and the health group were analyzed through the gene expression omnibus data set, and the related targets of hyperlipidemia were complemented using DrugBank, online Mendelian inheritance in man, GeneCards, DisGeNET and therapeutic target databases. Then, the protein-protein interaction network was constructed, the CytoNCA plugin and VarElect were used to screen core targets and metascape was used to systematically analyze the core targets and explore the mechanism. Finally, molecular docking showcased the interaction model. A total of 288 maslinic acid targets and 289 hyperlipidemia-related targets were collected and 18 potential therapeutic targets were found. The enrichment analysis results further systematically explained the effect of maslinic acid on hyperlipidemia. Maslinic acid can treat hyperlipidemia through complex interactions in which the regulation of core genes including albumin, peroxisome proliferator activated receptor alpha and apolipoprotein, and the regulation of peroxisome proliferator activated receptor signaling pathway play a major role.

Triterpenoids and triterpenoid saponins from leaves of Bougainvillea spectabilis

The genus Bougainvillea with about 18 species belonging to the family Nyctaginaceae is a widespread group throughout the world. Bougainvillea spectabilis was traditionally used in Indian and Mexico for treatment hepatitis, cough, and diarrhea. Ethanolic and methanolic extracts from leaves and stems of this plant showed anti–inflammatory activity. Some pharmacological studies have focused on antidiabetic activity of this species. Some extracts from leaves, bark exhibited hypoglycemic, -glucosidase, and amylase inhibitor activities. Phytochemical investigations have reported the isolation of flavonoids, triterpenoid saponins, and steroids. Leaves of B. spectabilis were collected and extracted with ethanol at room temperature by maceration method to obtain the ethanolic extract. By partitioning with n–hexane, ethyl acetate successively yields n–hexane and ethyl acetate extracts. Column chromatographies on normal phase silica gel, reversed–phase RP–18, and Sephadex LH–20 were used to isolate compounds 1–6. Their chemical structures were elucidated by HRESIMS, 1D, and 2D–NMR and compared with those reported in the literature, including lupeol (1), (20S)–3β–acetoxylupan–29–oic acid (2), maslinic acid (3), 3–O––D–(6'–O–methyl)glucuronopyranosyloleanolic acid (4), 3–O––D–(6'–O–ethyl)glucuronopyranosyloleanolic acid (5), and 3–O––D–glucopyranosyl–(14)––D–(6'–O–methyl)glucuronopyranosyloleanolic acid (6). All these compounds were isolated for the first time from the genus Bougainvillea.

Computational Prediction of Pharmacokinetic and Toxicological Properties ofSelected Phytochemicals from Eugenia jambolana Lam.

Background Eugenia jambolana Lam. is a herb distributed throughout the world and documented to possess many beneficial effects. The plant has been documented for the presence of various phytochemicals including primary and secondary metabolites.Aim of the Study In the present investigation an attempt has been made to carry out computational prediction of pharmacokinetic and toxicological properties of selected phytoconstituents from Eugenia jambolana Lam.Methodology We have selected oleanolic acid ursolic acid arjunolic acid maslinic acid corosolic acid asiatic acid alphitolic acid betulinic acid. PubChem database was utilized to collect the canonical smiles. Molsoft server was utilized to determine the drug likeness of selected phytochemicals. The admetSAR Structure Activity Relationship and Swiss ADME Absorption Distribution Metabolism and Excretion server were used for the determination of toxicity and pharmacokinetic properties.Results The results of investigation yielded the drug likeness score of selected phytoconstituents along with its pharmacokinetic and toxicity properties. The selected constituents such as Maslinic acid Arjunolic acid Oleanolic acid Ursolic acid Corosolic acid Asiatic acid Alphitolic acid Betulinic acid were found to be better drug like candidates.Conclusion The proposed In-silico work concluded that computer aided prediction and server based investigation was important and informative in collecting the data regarding drug like candidates and pharmacokinetic and toxicological properties of bioactive compounds from plant Eugenia jambolana Lam.

A Malaprade cleavage, a McMurry ring closure and an intramolecular aldol contraction of maslinic acid’s ring A

A silica gel supported Malaprade cleavage of methyl maslinoate (→3) followed by a titanium-on-graphite supported McMurry coupling was established to access a 2,12-terpenoid. The microwaves supported aldol reaction of dialdehyde 3 gave ring contracted 5. While parent maslinic acid is of minor cytotoxicity, improved cytotoxicity was observed in SRB assays for 3 while ring contracted compound 5 was most cytotoxic for MCF-7 breast adenocarcinoma cells holding a low EC50 = 3.1 μM.

Pentacyclic Triterpenoids, Phytosteroids and Fatty Acid Isolated from the Stem-bark of Cola lateritia K. Schum. (Sterculiaceae) of Cameroon origin; Evaluation of Their Antibacterial Activity

The phytochemical investigation on the chemical constituents of dichloromethane-methanol (1:1) stem-bark extract of Cola lateritia K. Schum. (Sterculiaceae) led to the isolation and characterization of five pentacyclic triterpenoids, one fatty acid and two phytosteroids. The compounds were identified as heptadecanoic acid ( 1 ), maslinic acid ( 2 ), betulinic acid ( 3 ), lupenone ( 4 ), lupeol ( 5 ), friedelin ( 6 ), β-stigmasterol ( 7 ) and ß -sitosterol-3 -O -ß- D -glucoside ( 8 ). Their structures were determined by NMR analysis ( 1 H, 13 C, DEPT-135, COSY, HMBC and HSQC), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with published data in the literature. This work, to the best of our knowledge, is the first isolation and identification of these compounds in pure forms from Cola lateritia . Also, compounds 1 – 3 are reported for the first time from Cola genus. In vitro antibacterial activity of the isolated compounds ( 1 – 8 ) and the crude extract were evaluated against Bacillus subtilis , Staphylococcus epidermidis , Enterococcus faecalis , Mycobacterium smegmatis , Staphylococcus aureus , Enterobacter cloacae , Klebsiella oxytoca , Proteus vulgaris , Klebsiella pneumonia , Escherichia coli, Proteus mirabilis and Klebsiella aerogenes with streptomycin, nalidixic acid and ampicillin as standard antibacterial drugs. Compound 2 was active against E. faecalis (MIC = 18.5 µg/mL), and it was 6.9 and 28 times lower and active than that of streptomycin (MIC 128 µg/mL) and nalidixic acid (MIC > 512 µg/mL) respectively. All the isolated compounds and crude extract showed significant activities against the tested bacterial strains.

Recent Advances on Anticancer Effects and Molecular Mechanisms of Maslinic Acid

Recent Advances on Anticancer Effects and Molecular Mechanisms of Maslinic Acid

Triterpenoids impede the fibrillation and cytotoxicity of human islet amyloid polypeptide

The inhibition of human islet amyloid polypeptide (hIAPP) deposition to block its toxicity is an important strategy for the prevention and treatment of type II diabetes mellitus (T2DM).Natural compounds with pharmacological properties and low toxicity can serve as a good point to discover potential inhibitors of protein misfolding, which may be useful for the treatment of various amyloidosis-related diseases. Previous studies have reported that triterpenoids, such as maslinic acid (MA) and momordicin I (MI), can modulate glucose metabolism partially by reducing insulin resistance. However, the internal antidiabetic mechanism of these triterpenoids remains unclear. In this study, we examined the inhibition and disaggregation of MAandits isomer MI on the fibrillation of hIAPP using various experimental and computational approaches. The assembly behaviors and peptide-induced cytotoxicity of hIAPP could be effectively resisted by MA and MI. Moreover, the interaction of the two triterpenoids with hIAPP displayed a spontaneous and exothermic process. Moreover, molecular dynamics simulation results of different peptides revealed that MA and MI could bind to Asn and other non-polar residues near the core C-terminal region and reduce the oligomerization of hIAPP. The binding affinity was predominantly contributed by hydrophobic, electrostatic and hydrogen bonding interactions. The present work provides valuable data for MA and MI to treat T2DM and amyloidosis-related diseases.