Quinovic Acid Research Articles

Evaluation of antimalarial compounds in Prosopis africana stem bark fractions against Plasmodium berghei

Prosopis africana, a traditional medicinal plant for malaria treatment, requires further scientific evidence. This study aimed to assess the antimalarial potential of Prosopis africana stem bark fractions in Plasmodium berghei-infected mice and identify the responsible compounds. The aqueous extract underwent partitioning with n-hexane, ethyl acetate, and methanol, followed by antimalarial evaluation. F5 was the most potent fraction based on its antimalarial potential. The study pooled 36 chromatographic separation sub-fractions into five using TLC analysis Rf values. In Plasmodium berghei-infected mice, fraction F5 at 6.25, 12.5, 25, and 50 mg/kg body weight (bw) was tested for antimalarial activity. Compound analysis of F5 utilized ultra-performance liquid chromatography-quadrupolar mass spectrometry. Statistical analysis employed Analysis of Variance and Duncan's multiple range tests (p < 0.05). The methanol, n-hexane, and ethylacetate extracts displayed suppression of P. berghei by 90%, 72.2%, and 73.6%, respectively. Methanol, n-hexane, and ethylacetate extracts suppressed P. berghei by 90%, 72.2%, and 73.6% respectively. F5 showed significantly higher chemo-suppression (67.21%) than F1 (63.94%), F2 (6.99%), F3 (2.81%), and F4 (37.3%). At 12.5 mg/kg bw, F5 suppressed P. berghei by 91.09%, surpassing chloroquine (87.79%), and restored altered hematological indices and CD4+ counts. Compounds identified in F5 included caffeate, linalool, terpinene-4-ol, quinovic acid, quercetin, prosopinine, catechin, and apigeninin. In conclusion, the fraction F5 of P. africana stem bark exhibited higher antimalarial activity than chloroquine and the identified compound might likely contribute to its activity.

Comprehensive In Silico Analysis of Uncaria Tomentosa Extract: Chemical Profiling, Antioxidant Assessment, and CLASP Protein Interaction for Drug Design in Neurodegenerative Diseases.

Uncaria tomentosa is a traditional medicinal herb renowned for its anti-inflammatory, antioxidant, and immune-enhancing properties. In the realm of neurodegenerative diseases (NDDS), CLASP proteins, responsible for regulating microtubule dynamics in neurons, have emerged as critical players. Dysregulation of CLASP proteins is associated with NDDS, such as Alzheimer's, Parkinson's, and Huntington's diseases. Consequently, comprehending the role of CLASP proteins in NDDS holds promise for the development of innovative therapeutic interventions. The objectives of the research were to identify phytoconstituents in the hydroalcoholic extract of Uncaria tomentosa (HEUT), to evaluate its antioxidant potential through in vitro free radical scavenging assays and to explore its potential interaction with CLASP using in silico molecular docking studies. HPLC and LC-MS techniques were used to identify and quantify phytochemicals in HEUT. The antioxidant potential was assessed through DPPH, ferric reducing antioxidant power (FRAP), nitric oxide (NO) and superoxide (SO) free radical scavenging methods. Interactions between conventional quinovic acid, chlorogenic acid, epicatechin, corynoxeine, rhynchophylline and syringic acid and CLASP were studied through in silico molecular docking using Auto Dock 4.2. The HEUT extract demonstrated the highest concentration of quinovic acid derivatives. HEUT exhibited strong free radical-scavenging activity with IC50 values of 0.113 μg/ml (DPPH) and 9.51 μM (FRAP). It also suppressed NO production by 47.1 ± 0.37% at 40 μg/ml and inhibited 77.3 ± 0.69% of SO generation. Additionally, molecular docking revealed the potential interaction of quinovic acid with CLASP for NDDS. The strong antioxidant potential of HEUT and the interaction of quinovic acid with CLASP protein suggest a promising role in treating NDDS linked to CLASP protein dysregulation.

Tetraenone A: A New β-Ionone Derivative from Tetraena aegyptia.

In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2S, 5R, 6R, 7E)-2-hydroxy-5,6-dihydro-β-ionone) (1), along with (3S, 5R, 6S, 7E)-3-hydroxy-5,6-epoxy-5,6-dihydro-β-ionone- (2), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside (3), 3β,19α-dihydroxy-ursan-28-oic acid (4), quinovic acid (5), p-coumaric acid (6), and ferulic acid (7), for the first time. The chemical structures of 1-7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with Mpro rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with Mpro to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of Mpro of SARS-CoV-2.

Diverse mitochondrial effects, antiplasmodial and anti-inflammatory potentials of Costus afer (Ker Gawl), Nauclea latifolia (Sm) and Sphenocentrum jollyanum (Pierre) in mice infected with Plasmodium berghei

ObjectivesThis study reported the antiplasmodial, anti-inflammatory and mito-protrective effects of Costus afer (CA), Nauclea latifolia (NA) and Sphenocentrum jollyanum (SJ) methanol extracts in Plasmodium berghei-infected mice. MethodsAir-dried CA, NA and SJ were extracted with methanol. Antiplasmodial activity of these extracts were monitored using chloroquine-sensitive and resistant strains of Plasmodium berghei. Heme and hemozoin contents, interleukins and C-reactive protein as well as mitochondrial permeability transition (mPT) pore opening, lipid peroxidation (mLPO) and F0F1 ATPase activity were determined by spectrophotometry. Phytochemical constituents were determined using UPLC-QTOF-MS and NMR spectroscopy. Results and ConclusionsCA, NL and SJ decreased percentage parasitemia to 0.25 ± 0.07; 0.30 ± 0.14 and 0.25 ± 0.07% relative to control (8.60 ± 0.15%) in the chloroquine-sensitive model and to 0.40 ± 0.14; 0.30 ± 0.14 and 0.45 ± 0.07, respectively as against 10.88 ± 0.26% of the infected control in the chloroquine-resistant model. In chloroquine-resistant model, NL decreased mLPO (0.41 ± 0.04) F0F1 ATPase (0.15 ± 0.02 mmol pi/mg protein /min) while CA enhanced mPT pore opening at 100 mg/kg,and SJ (50 mg/kg) reversed parasite-induced mPT pore opening (1.66 vs 9.4 folds). The NL increased heme, decreased hemozoin, IL-6, CRP, TNF-α, while SJ dose-dependently increased IL-10. UPLC-QTOF-MS analysis showed that coumaric acid, divaricatinic acid, diocin and aferiosides A and C were present in CA, 3-caffeoylquinic acid, 18, 19-dihydroangustine, jatrorrhizine, 17-epinaucleidinal, strictosamide and quinovic acid 3-O-rhamnoside in NL and quinic acid, jatrorrhizine and mabioside B in SJ. While the three medicinal plants have varying antimalarial effects, their decoction will be better for a synergistic purpose.

A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition.

Phytochemical study of the ethyl acetate root extract of Zygophyllum album has resulted in the isolation of a new saponin, Zygo-albuside D (1), along with two known compounds; (3-O-[β-D-quinovopyranosyl]-quinovic acid) (2), which is first reported in the root, and catechin (3), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin (1) exhibited promising cytotoxicity with IC50 values of 3.5 and 5.52 μM on A549 and PC-3 cancer cell lines, respectively, compared to doxorubicin with IC50 values of 9.44 and 11.39 μM on A549 and PC-3 cancer cell lines, respectively. While it had an IC50 value of 46.8 μM against WISH cells. Investigating apoptosis-induction, compound 1 induced total apoptotic cell death in A549 lung cancer cells by 32-fold; 21.53% compared to 0.67% in the untreated control cells. Finally, it upregulated the pro-apoptotic genes and downregulated the antiapoptotic gene using gene expression levels. Compound 1 exhibited remarkable CDK-2 target inhibition by 96.2% with an IC50 value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound 1 as CDK2 and Bcl2 inhibitors that led to apoptosis induction in A549 cancer cells. Hence, this study highlights the importance of compound 1 in the design of a new anticancer agent with specific mechanisms.

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég).

Background: Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. Aim: The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. Results: Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. Conclusion: Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.

Screening and selection of formulation components of nanostructured lipid carriers system for Mitragyna Speciosa (Korth). Havil drug delivery

Nanostructured lipid carriers (NLC) have evolved as effective vehicles for improving the bioavailability of poorly water-soluble drugs as well as protecting them from degradation and metabolism. The present study investigated the preformulation and its impact on different liquid lipids and solid lipids with diverse chemical structures and hydrophilic-lipophilic balance (HLB) for the critical quality attributes of Mitragyna speciosa leaves extract (MS)-based nanostructured lipid carriers suitable for drug delivery system. The presence of bioactive alkaloids (mitragynine, 7-hydroxymitragynine, speciogynine), flavonoids (quercetin, apigenin, kaempferol), saponins (daucosterol, quinovic acid 3-o-beta-d-quinovopyranoside, 1-o-feruloyl-beta-d-glucose), and other bioactive phytochemicals (chlorogenic acid, umbelliferone, ursolic acid) in MS leaves extract was detected using LCMS/MS analysis to support its medicinal properties. The total phenolic content, total flavonoid content, and DPPH assay of MS were 90.88 ± 0.30 GAE mg/g, 50.43 ± 0.47 QE mg/g, and IC50 at 0.0397 ± 0.0035 mg/mL, respectively. The screening preparation of NLC requires the selection of liquid lipid (oil), solid lipid, and surfactant. Based on the solubility test, the maximum solubility of MS leaves extract in oleic acid (liquid lipid) and compritol ATO 888 (solid lipid) were 2.859 ± 0.010% and 53.02 ± 0.39% respectively at ratio 70:30. Tween 80 was selected as the main surfactant for the preparation of NLC due to its highest emulsification efficiency (51.53%). The antimicrobial study showed that MS leaves extract gives antimicrobial effect towards Streptococcus aureus bacteria. The preformulation information collected offers a better, efficient, and cost-effective choice for further formulation development of MS leaves extract in drug delivery systems.

Bioguided Fractionation and Isolation of an Antiplasmodial Saponin from the Roots of Nauclea xanthoxylon (A.Chev.) Aubrév. (Rubiaceae).

The root extract of Nauclea xanthoxylon (A.Chev.) Aubrév. displayed significant 50 % inhibition concentration (IC50 s) of 0.57 and 1.26 μg/mL against chloroquine resistant and sensitive Plasmodium falciparum (Pf) Dd2 and 3D7 strains, respectively. Bio-guided fractionation led to an ethyl acetate fraction with IC50 s of 2.68 and 1.85 μg/mL and subsequently, to the new quinovic acid saponin named xanthoxyloside (1) with IC50 s of 0.33 and 1.30 μM, respectively against the tested strains. Further compounds obtained from ethyl acetate and hexane fractions were the known clethric acid (2), ursolic acid (3), quafrinoic acid (4), quinovic acid (5), quinovic acid 3-O-β-D-fucopyranoside (6), oleanolic acid (7), oleanolic acid 3-acetate (8), friedelin (9), β-sitosterol (10a), stigmasterol (10b) and stigmasterol 3-O-β-D-glucopyranoside (11). Their structures were characterised with the aid of comprehensive spectroscopic methods (1 and 2D NMR, Mass). Bio-assays were performed using nucleic acid gel stain (SYBR green I)-based fluorescence assay with chloroquine as reference. Extracts and compounds exhibited good selectivity indices (SIs) of >10. Significant antiplasmodial activities measured for the crude extract, the ethyl acetate fraction and xanthoxyloside (1) from that fraction can justify the use of the root of N. xanthoxylon in ethnomedicine to treat malaria.

Inhibition of Advanced Glycation End-Products by Tamarindus indica and Mitragyna inermis Extracts and Effects on Human Hepatocyte and Fibroblast Viability

Tamarindus indica and Mitragyna inermis are widely used by herbalists to cure diabetes mellitus. The aim of this study is to investigate the inhibitory potential of aqueous and various organic solvent fractions from both plants and some isolated compounds against advanced glycation end-products (AGEs). For this purpose, an in vitro BSA-fructose glycation model was used to evaluate the inhibition of AGE formation. Furthermore, the effects of the fractions on mouse fibroblast (NIH-3T3) and human hepatocyte (HepG2) survival were evaluated. The leaf, stem, and root fractions of both plants exhibited significant inhibition of AGEs formation. The IC50 values appeared to be less than 250 µg/mL; however, all fractions presented no adverse effects on NIH-3T3 up to 500 µg/mL. Otherwise, our phytochemical investigation afforded the isolation of a secoiridoid from the Mitragyna genus named secoiridoid glucoside sweroside (1), along with three known quinovic acid glycosides: quinovic acid-3β-O-β-d-glucopyranoside (2), quinovic acid-3-O-β-d-6-deoxy-glucopyranoside, 28-O-β-d-glucopyranosyl ester (3), and quinovic acid 3-O-α-l-rhamnopyranosyl-(4→1)-β-d-glucopyranoside (4). In particular, 1-3 are compounds which have not previously been described in Mitragyna inermis roots. However, the isolated compounds did not exhibit AGE inhibitory activity. Further investigation on these potent antiglycation fractions may allow for the isolation of new antidiabetic drug candidates.

Isolation, Cytotoxicity Evaluation, Docking, ADMET and Drug Likeness Studies of Secondary Metabolites from the Stem Bark ofAnthocephalus cadamba(Roxb.)

AbstractPhytochemical investigation of the stem bark ofAnthocephalus cadamba(Rubiaceae) led to the isolation of total ten secondary metabolites (1‐10) including β–sitosterol (1), ursolic acid (2), vanillic acid (3), quinovic acid (4), 3‐O‐[α‐L‐rhamnopyranosyl]‐quinovic acid (5), β‐sitosterol β‐D‐glucoside (6), cadambine (7), 3β‐dihydrocadambine (8), 7‐O‐acetyl loganin (9) and hexylp‐coumarate (10). Four acetylated derivatives2 a,5 a,7 aand8 aobtained through acetylation of compounds2,5,7and8respectively. All the compounds characterized using1H and13CNMR, HRESIMS and IR and comparison with literature. Compound4showed the best cytotoxic activity with IC50value 4 and 7 μM against pancreatic (MIA‐pa‐Ca‐2) and leukemia (HL‐60) cancer cells respectively. Docking results supported the anticancer potential of compound4viainhibition of EGFR receptor (PDB ID:3POZ) and its pharmacokinetic profile found optimized as per the Lipinski's filter. Therefore compound4has the potential to be developed as an anticancer agent against pancreatic cancer cells.

Chemotaxonomy and Antibacterial Activity of the Extracts and Chemical Constituents of Psychotria succulenta Hiern. (Rubiaceae).

The use of natural products for medicinal purposes is becoming more and more common nowadays, as evidenced by the presence in plants of secondary metabolites with different potentials such as antioxidant and antibacterial properties. We evaluated in this work the antimicrobial activities of the extracts and some isolated compounds from the seeds of Psychotria succulenta Hiern. (Rubiaceae), a Cameroonian medicinal plant traditionally used to cure microbial infections. The ethanol extract was prepared by maceration and extracted with ethyl acetate and n-butanol. The EtOAc (m = 168 g) and n-BuOH (m = 20 g) extracts were further fractionated by silica gel column chromatography to isolation of compounds. Their structures were elucidated by spectroscopic analysis and by comparison with published data. The antibacterial activity of extracts and compounds was assessed by evaluating the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against pathogenic bacteria. Thirteen compounds including four alkaloids (veprisine (1), naucleofficine III (2), vepridimerine B (3), and vepridimerine C (4)), three triterpenes (barbinervic acid (5), 3-O-α-L-rhamnopyranosyl quinovic acid (6), and oleanolic acid (7)), one steroid (β-sitosterol-3-O-β-D-glucopyranoside (8)), four phenolic compounds (scopoletin (9), gallic acid (10), quercetin-3-O-β-D-glucopyranoside (11), and kaempferol 3-O-α-L-rhamnopyranoside-7-O-α-L-rhamnopyranoside (12)), and one iridoid (borreriagenin (13)) were isolated from the EtOAc and n-BuOH extracts. These compounds were identified by 1D and 2D NMR combined analysis as well as by melting point comparison. The EtOH, EtOAc, and n-BuOH extracts exhibited significant antibacterial activities (MIC = 32‐128 μg/mL; MBC = 64‐256 μg/mL) against Staphylococcus aureus (Gram-positive bacterium), Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia (Gram-negative bacteria). Among the isolated compounds, scopoletin (9) showed a moderate activity against Klebsiella pneumoniae with MIC and MBC values of 16 μg/mL and 32 μg/mL, respectively. It appears that, chemotaxonomically, some of the isolated compounds have already been obtained from the genus Psychotria but to the best of our knowledge, this is the first report on the phytochemical investigation of P. succulenta. Although many other studies need to be achieved, our results support the use of P. succulenta in traditional medicine to cure infectious diseases particularly those caused by the tested bacteria.

Recurvataside, a new saponin from aerial parts of Mussaenda recurvata

A new glycoside, recurvataside (1) and six known compounds, quinovic acid (2), quinovic acid 28-O-β-D-glucopyranosyl ester (3), 3-O-β-D-glucopyranosylquinovic acid (4), 3-O-β-D-glucopyranosylquinovic acid 28-O-β-D-glucopyranosyl ester (5), pomolic acid (6), and ursolic acid (7) were isolated from aerial parts of Mussaenda recurvata. The structure of compound 1 was identified from its spectroscopic data and by comparison with the literature. Recurvataside represents the first occurrence of δ-oleanolic acid saponin bearing two D-glucose units at C-3 and C-28 in nature. This is the first time δ-oleanane-type saponin reported in the genus Mussaenda. Compounds 1-7 were evaluated the cytotoxicity against two cancer cell lines MCF-7 and HepG2. Among them, only compound 7 exhibited moderate activity against MCF-7 and HepG2 cell lines with IC50 value of 16.97 ± 1.55 and 20.28 ± 1.00 μM, respectively. Compounds 1–7 were also tested for their inhibitory NO production in LPS-stimulated RAW264.7 cells. Compounds 3, 5, and 7 showed significant reduction of nitrite accumulation in LPS-stimulated RAW 264.7 cells with the IC50 values of 8.81 ± 0.48, 13.42 ± 0.84, and 18.37 ± 0.67 μM, respectively.

Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatases/ Phosphodiesterases (PDEs).

Phosphodiesterases (PDEs) are a wide group of enzymes with multiple therapeutic actions, including vasorelaxation, cardiotonic, antidepressant, anti-inflammatory, antithrombotic, anti-spasmolytic, memory-enhancing, and anti-asthmatic. PDEs with eleven subtypes from PDE-1 to PDE-11 typically catalyze the cleavage of the phosphodiester bond and, hence, degrades either cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP). Several selective or non-selective inhibitors of the PDE subtypes are used clinically, i.e. sildenafil, rolipram, cysteine, etc. Recently, interest in plant-based pharmacologically bioactive compounds having potent PDEs inhibitory potential has increased. Purposely, extensive research has been carried out on natural products to explore new inhibitors of various PDEs. Therefore, this review summarizes the published data on natural PDEs inhibitors and their potential therapeutic applications. For this purpose, natural compounds with PDE inhibitory potential have been surveyed through several databases, including PubMed, Web of Sciences (WoS), Scopus, and Google Scholar. According to a detailed literature survey, the most promising class of herbal compounds with PDE-inhibiting property has been found to belong to phenolics, including flavonoids (luteolin, kaempferol, icariin, etc.). Many other encouraging inhibitors from plants have also been identified, such as coumarins (23, 24) (licoarylcoumarin and glycocoumarin,), saponins (agapanthussaponins), lignans (31, 33) [(±)-schizandrin and kobusin], terpenes (28, 29, 31) (perianradulcin A, quinovic acid, and ursolic acid), anthraquinones (18, 19) (emodin and chrysophanol), and alkaloids (Sanjoinine-D) (36). In this review, studies have revealed the PDE-inhibitory potential of natural plant extracts and their bioactive constituents in treating various diseases; however, further clinical studies comprising synergistic use of different therapies (synthetic & natural) to acquire multi-targeted results might also be a promising option.

Genome-Wide Identification of OSC Gene Family and Potential Function in the Synthesis of Ursane- and Oleanane-Type Triterpene in Momordica charantia.

The triterpenes in bitter gourd (Momordica charantia) show a variety of medicinal activities. Oxidosqualene cyclase (OSC) plays an indispensable role in the formation of triterpene skeletons during triterpene biosynthesis. In this study, we identified nine genes encoding OSCs from bitter gourd (McOSC1–9). Analyses of their expression patterns in different tissues suggested that characteristic triterpenoids may be biosynthesized in different tissues and then transported. We constructed a hairy root system in which McOSC7 overexpression led to an increased accumulation of camaldulenic acid, enoxolone, and quinovic acid. Thus, the overexpression of McOSC7 increased the active components content in bitter gourd. Our data provide an important foundation for understanding the roles of McOSCs in triterpenoid synthesis.

New combination approaches to combat methicillin-resistant Staphylococcus aureus (MRSA)

The herbal products proved to be more promising antimicrobials even though their antimicrobial activity is milder than commercially available antibiotics. Moreover, herbal drugs may act synergistically with antibiotics to kill microbes. In this study, we aimed to enhance the activity of penicillin against MRSA through combination with the active saponin fraction isolated from the Zygophyllum album plant. Three different types of metabolites (saponins, sterols, and phenolics) have been extracted from Zygophyllum album with ethanol and purified using different chromatographic techniques. The antibacterial activity of crude extract and the separated metabolites were checked against MRSA isolates, Saponin fraction (ZA-S) was only the active one followed by the crude extract. Therefore, the compounds in this fraction were identified using ultra-high-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) operated in positive and negative ionization modes. UHPLC/QTOF-MS revealed the presence of major six ursane-type tritepenoidal saponins (Quinovic acid, Quinovic acid 3β-O-β-D-quinovopyranoside, Zygophylloside C, Zygophylloside G, Zygophylloside K and Ursolic acid), in addition to Oleanolic acid. Interaction studies between saponin fraction and penicillin against MRSA were performed through the checkerboard method and time-kill assay. According to checkerboard results, only three combinations showed a fractional inhibitory concentration index less than 0.5 at concentrations of (62.5 + 312.5, 62.5 + 156.25, and 62.5 + 78.125 of penicillin and ZA-S, respectively). Time kill assay results showed that the highest reduction in log10 colony-forming unit (CFU)/ml of initial inoculum of MRSA after 24 h occurred by 3.7 at concentrations of 62.5 + 312.5 (µg/µg)/ml of penicillin and ZA-S, respectively. Thus, the combination between saponin fraction of Zygophyllum album and penicillin with these concentrations could be a potential agent against MRSA that can serve as possible model for new antibacterial drug.

Quinovic Acid Impedes Cholesterol Dyshomeostasis, Oxidative Stress, and Neurodegeneration in an Amyloid-β-Induced Mouse Model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder typified by several neuropathological features including amyloid-beta (Aβ) plaque and neurofibrillary tangles (NFTs). Cholesterol retention and oxidative stress (OS) are the major contributors of elevated β- and γ-secretase activities, leading to excessive Aβ deposition, signifying the importance of altered cholesterol homeostasis and OS in the progression of Aβ-mediated neurodegeneration and cognitive deficit. However, the effect of Aβ on cholesterol metabolism is lesser-known. In this study, we evaluated the effect of quinovic acid (QA; 50 mg/kg body weight, i.p.) against the intracerebroventricular (i.c.v.) injection of Aβ (1-42)-induced cholesterol dyshomeostasis, oxidative stress, and neurodegeneration in the cortex and hippocampal brain regions of wild-type male C57BL/6J mice. Our results indicated that Aβ (1-42)-treated mice have increased Aβ oligomer formation along with increased β-secretase expression. The enhanced amyloidogenic pathway in Aβ (1-42)-treated mice intensified brain cholesterol accumulation due to increased expressions of p53 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme. Importantly, we further confirmed the p53-mediated HMGCR axis activation by using pifithrin-α (PFT) in SH-SY5Y cells. Furthermore, the augmented brain cholesterol levels were also associated with increased OS. However, the QA administration to Aβ (1-42)-injected mice significantly ameliorated the Aβ burden, p53 expression, and cholesterol accumulation by deterring the oxidative stress through upregulating the Nrf2/HO-1 pathway. Moreover, the QA downregulated gliosis, neuroinflammatory mediators (p-NF-κB and IL-1β), and the expression of mitochondrial apoptotic markers (Bax, cleaved caspase-3, and cytochrome c). QA treatment also reversed the deregulated synaptic markers (PSD-95 and synaptophysin) and improved spatial learning and memory behaviors in the Aβ-treated mouse brains. These results suggest that Aβ (1-42) induces its acute detrimental effects on cognitive functions probably by increasing brain cholesterol levels through a possible activation of the p53/HMGCR axis. However, QA treatment reduces the cholesterol-induced oxidative stress, neuroinflammation, and neurodegeneration, leading to the restoration of cognitive deficit after Aβ (1-42) i.c.v. injection in mice.

In Silico ADMET Evaluation of Natural DPP-IV Inhibitors for Rational Drug Design against Diabetes.

As a metabolic and lifestyle disorder, diabetes mellitus poses a prodigious health risk. Out of the many key targets, DPP-IV is one of the very imperative therapeutic targets for the treatment of diabetic patients. In our current study, we have done the in silico simulations of ADME-T properties for naturally originated potent DPP-IV inhibitors like quinovic acid, stigmasterol, quinovic acid-3-beta-D-glycopyranoside, zygophyloside E, and lupeol. Structural topographies associated with different pharmacokinetic properties have been systematically assessed. Glycosylation on quinovic acid is found to be noteworthy for the improvement of pharmacokinetic and toxicological properties, which leads to the prediction that zygophyloside E can be further tailored down to get the lead DPP-IV inhibitor. This assessment provides useful insight into the future development of novel drugs for the treatment of diabetes mellitus.

Quinovic acid purified from medicinal plant Fagonia indica mediates anticancer effects via death receptor 5.

Plants are major source for discovery and development of anticancer drugs. Several plant-based anticancer drugs are currently in clinical use. Fagonia indica is a plant of medicinal value in the South Asian countries. Using mass spectrometry and NMR spectroscopy, several compounds were purified from the F. indica extract. We have used one of the purified compounds quinovic acid (QA) and found that QA strongly suppressed the growth and viability of human breast and lung cancer cells. QA did not inhibit growth and viability of non-tumorigenic breast cells. QA mediated its anticancer effects by inducing cell death. QA-induced cell death was associated with biochemical features of apoptosis such as activation of caspases 3 and 8 as well as PARP cleavage. QA also upregulated mRNA and protein levels of death receptor 5 (DR5). Further investigation revealed that QA did not alter DR5 gene promoter activity, but enhanced DR5 mRNA and protein stabilities. DR5 is one of the major components of the extrinsic pathway of apoptosis. Accordingly, Apo2L/TRAIL, the DR5 ligand, potentiated the anticancer effects of QA. Our results indicate that QA mediates its anticancer effects, at least in part, by engaging DR5-depentent pathway to induce apoptosis. Based on our results, we propose that QA in combination with Apo2L/TRAIL can be further investigated as a novel therapeutic approach for breast and lung cancers.

Protein tyrosine phosphatase 1B inhibitory triterpene glycosides from Mussaenda pilosissima Valeton

Three new triterpene glycosides, mussapilosides A–C (1-3) together with six known triterpene glycosides, cincholic acid-28-O-β-d-glucopyranosyl ester (4), mussaendoside S (5), quinovic acid 28-O-β-d-glucopyranosyl ester (6), glycoside A (7), glycoside B (8), and quinovic acid 3-O-β-d-glucopyranosyl(1→2)-β-d-glucopyranoside (9) were isolated from the leaves of Mussaenda pilosissima. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR, and HR ESI MS spectra. All these compounds were examined for their inhibitory activity against PTP1B. The results indicated that compounds 2, 6, and 8 exhibited potent inhibitory effects with IC50 values of 3.4 ± 0.2, 4.2 ± 0.2, and 6.4 ± 0.2 μM, respectively. Compound 5 showed the moderate inhibitory effect with IC50 value of 63.0 ± 3.2 μM.

A Rare Triterpenoidal Saponin Isolated and Identified fromTetraena simplex(L.) Beier &Thulin (Syn.Zygophyllum simplexL.)

AbstractTetraena simplex(L.) Beier & Thulin (syn.Zygophyllum simplexL.) is an annual, succulent plant belonging to family Zygophyllaceae. The plant grows in harsh environmental conditions and it is traditionally used as an analgesic and anti‐inflammatory agent. This study aims to isolate and identify phytochemical constituents of then‐butanol fraction of its aerial parts that was repeatedly chromatographed on Diaion HP‐20 and silica gel columns to yield a rare triterpenoidal saponin, 3‐O‐[β‐D‐glucopyranosyl‐(1→2)‐β‐D‐glucopyranosyl] quinovic acid‐28‐O‐β‐D‐glucopyranosyl ester (1) along with three other known triterpenoidal compounds namely; 3‐O‐methoxy‐quinovic acid (2), quinovic acid (3), and 3‐O‐β‐D‐glucopyranosyl‐quinovic acid (4). Moreover, quercetin 3‐O‐α‐L‐rhamnoside (5) was isolated from this fraction. Different spectroscopic techniques including one dimensional (1D) and two dimensional (2D) NMR (Nuclear Magnetic Resonance) spectroscopy allowed the unambiguous structure elucidation of the isolated compounds.