Modified ent-Abietane Diterpenoids from the Leaves of Suregada zanzibariensis.

The leaf extract of Suregada zanzibariensis gave two new modified ent-abietane diterpenoids, zanzibariolides A (1) and B (2), and two known triterpenoids, simiarenol (3) and ß-amyrin (4). The structures of the isolated compounds were elucidated based on NMR and MS data analysis. Single-crystal X-ray diffraction was used to establish the absolute configurations of compounds 1 and 2. The crude leaf extract inhibited the infectivity of herpes simplex virus 2 (HSV-2, IC50 11.5 µg/mL) and showed toxicity on African green monkey kidney (GMK AH1) cells at CC50 52 µg/mL. The isolated compounds 1-3 showed no anti-HSV-2 activity and exhibited insignificant toxicity against GMK AH1 cells at ≥100 µM.

The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents.

Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes' therapeutic effects and the development of new topical formulations.

Commikuanoids A-C: New cycloartane triterpenoids with exploration of carbonic anhydrase-II inhibition from the resins of Commiphora kua by in vitro and in silico molecular docking.

Three new cycloartane triterpenoids, commikuanoids A-C (1-3), together with four known compounds 4-7, were isolated from the resin of Commiphora kua. Their structures were confirmed by advanced NMR techniques such as 1D (1H and 13C) and 2D (HMBC, HSQC, COSY, NOESY and NOE) and high-resolution mass spectrometry (HRMS). Five compounds (1-5) were screened for in vitro carbonic anhydrase II (CA II) inhibitory activity. All the tested compounds demonstrated significant activity against CA II with IC50 values ranging from 4.9-19.6 µM. Moreover, the binding pattern of each compound in the binding site of CA-II was predicted through in silico molecular docking approach. It was observed that compounds 2, 4, and 5 binds with the Zn ion present in the active site of CA II, while compounds 1 and 3 mediated hydrogen bonding with Thr199 of CA-II, and all the compounds showed good binding score (> - 5 kcal/mol).

Wound healing, anti-inflammatory and anti-melanogenic activities of ursane-type triterpenes from Semialarium mexicanum (Miers) Mennega.

ETHNO-PHARMACOLOGICAL RELEVANCE: The bark of Semialarium mexicanum commonly known as 'Cancerina' is used as an infusion in Central America and Mexico to treat various wound infections, as well as skin and vaginal ulcers. AIM OF THE STUDY: This study aimed to determine the wound healing, anti-inflammatory and anti-melanogenic activities of the aqueous extract of Semialarium mexicanum and to identify the compounds related to these activities. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Semialarium mexicanum was carried out, selecting the sub-extracts and fractions depending on their wound healing, anti-inflammatory and anti-melanogenic activities in the RAW 264.7, NIH/3T3 and B16-F10 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3ß)-3-Hydroxy-urs-12-en-28-oic acid (1), (3ß)-Urs-12-ene-3,28-diol (2) and (2α, 19α)-2,19-Dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Regarding the anti-inflammatory activity, the three compounds inhibited the production of NF-κB and NO, however, compound 3 was the most active with IC50 values of 8.15-8.19 µM and 8.94-9.14 µM, respectively, in all cell lines. The anti-melanogenic activity of these compounds was evaluated by the inhibition of tyrosinase and melanin in the B16-F10 cell line. The three compounds showed anti-melanogenic activity, however, compound 3 was the most active with an IC50 of 8.03 µM for the inhibition of tyrosinase production, and an IC50 of 8.53 µM for the inhibition of melanin production. Finally, concerning the wound healing activity, the three compounds presented proliferative activity in all the tested cell lines, however, compound 3 showed higher cell proliferation percentages than compounds 1 and 2 (88.89-89.60% compared to 64.92-65.71% and 71.53-71.99%, respectively). CONCLUSION: The wound healing, anti-inflammatory and anti-melanogenic activity of the aqueous extract of Semialarium mexicanum was tested and analysed in the present study, after having isolated three ursane-type triterpenes.

Intestinal absorption mechanism of rotundic acid: Involvement of P-gp and OATP2B1.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilicis Rotundae Cortex (IRC), the dried barks of Ilex rotunda Thunb. (Aquifoliaceae), has been used for the prevention or treatment of colds, tonsillitis, dysentery, and gastrointestinal diseases in folk medicine due to its antibacterial and anti-inflammatory effects. However, there is no report about the intestinal absorption of major compounds that support traditional usage. AIM OF STUDY: Considering the potential of rotundic acid (RA) - major biologically active pentacyclic triterpenes found in the IRC, this study was purposed to uncover the oral absorption mechanism of RA using in situ single-pass intestinal perfusion (SPIP) model, in vitro cell models (Caco-2, MDCKII-WT, MDCKII-MDR1, MDCKII-BCRP, and HEK293-OATP2B1 cells) and in vivo pharmacokinetics studies in rats. MATERIALS AND METHODS: The molecular properties (solubility, lipophilicity, and chemical stability) and the effects of principal parameters (time, compound concentrations, pH, paracellular pathway, and the different intestinal segments) were analyzed by liquid chromatography-tandem mass spectrometry. The susceptibility of RA to various inhibitors, such as P-gp inhibitor verapamil, BCRP inhibitor Ko143, OATP 2B1 inhibitor rifampicin, and absorption enhancer EGTA were assessed. RESULTS: RA was a compound with low water solubility (12.89 µg/mL) and strong lipophilicity (LogP = 4.1). RA was considered stable in all media during the SPIP and transport studies. The SPIP and cell experiments showed RA was moderate absorbed in the intestines and exhibited time, concentration, pH, and segment-dependent permeability. In addition, results from the cell model, in situ SPIP model as well as the in vivo pharmacokinetics studies consistently showed that verapamil, rifampicin, and EGTA might have significant effect on the intestinal absorption of RA. CONCLUSION: The mechanisms of intestinal absorption of RA might involve multiple transport pathways, including passive diffusion, the participation of efflux (i.e., P-gp) and influx (i.e., OATP2B1) transporters, and paracellular pathways.

The chemical composition of different leaf extracts of Lantana fucata Lindl. influences its cytotoxic potential: A study using the Allium cepa model.

ETHNOPHARMACOLOGICAL RELEVANCE: One of the most popular plants used to treat diseases in Brazil is Lantana fucata. Like most herbal medicines, its consumption is based on popular knowledge, which, despite being considered effective, may cause side effects. AIM OF THE STUDY: Since the scientific data on the pharmacological properties of L. fucata are still incipient, this research aimed to evaluate the cytotoxic and genotoxic potential of different types of extracts (infusion, aqueous and hydroalcoholic), characterizing them chemically. MATERIALS AND METHODS: The cytotoxicity assay was performed by the A. cepa model. The cytotoxicity parameters studied were number of dividing cells and percentage mitotic index (%MI). RESULTS: The result of the A. cepa assay showed that there was a decrease in the number of dividing cells and the percentage mitotic index as concentrations increased, for all extracts, indicating cytotoxicity. However, the hydroalcoholic extract was the most cytotoxic. Chromatography analysis allowed the characterization of secondary metabolites in the extracts, which were very similar. However, a greater abundance of flavonoids and triterpenoids was observed in the hydroalcoholic extract, suggesting that these compounds are responsible for its greater toxicity. CONCLUSIONS: Since the highest doses of extracts showed to have a cytotoxic effect, it is suggested that the ingestion of this species occurs in a moderate way.

21,24-Cyclolanostanes revisited: Structural revision and biological evaluation.

Chemical fractionation of the EtOH extract of a medicinal macro fungus, Inonotus obliquus, afforded an array of lanostane-type triterpenoids (1-11) including two new ones (1 and 8). The structures of these compounds were determined on the basis of spectroscopic analyses, single crystal X-ray crystallography of 3-6 and biosynthetic considerations. With the confirmatory structural information provided by X-ray diffraction analysis in hand, several previously reported 21,24-cyclolanostanes, such as inonotsutriols A-C and (20R,21S,24S)-21,24-cyclopenta-3ß,21,25-trihydroxylanosta-8-ene, were structurally corrected. In addition, the NMR data of other types of 21,24-cyclo triterpenoids were also re-examined and structural revisions were thus suggested. Compounds 2, 6 and 8 showed significant cytostatic effects against a panel of tumor cell lines with IC50 values ranging from 7.80 to 18.5 µM. Further assays established that compound 2 exerted promising in vitro anti-breast cancer potential by inhibiting the proliferation and migration of 4T1 cells.

The triterpenoids and sesquiterpenoids from the plant of Agrimonia pilosa.

A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19ß-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC50 values of 16.31 µM, 21.94 µM, and 23.40 µM, respectively.

The protective effect of Centella asiatica and its constituent, araliadiol on neuronal cell damage and cognitive impairment.

Alzheimer's disease (AD) is characterized by progressive cognitive decline, and the number of affected individuals has increased worldwide. However, there are no effective treatments for AD. Therefore, it is important to prevent the onset of dementia. Oxidative stress and endoplasmic reticulum (ER) stress are increased in the brains of AD patients, and are postulated to induce neuronal cell death and cognitive dysfunction. In this study, Centella asiatica, a traditional Indian medicinal herb, were fractionated and compared for their protective effects against glutamate and tunicamycin damage. Araliadiol was identified as a component from the fraction with the highest activity. Further, murine hippocampal cells (HT22) were damaged by glutamate, an oxidative stress inducer. C. asiatica and araliadiol suppressed cell death and reactive oxygen species production. HT22 cells were also injured by tunicamycin, an ER stress inducer. C. asiatica and araliadiol prevented cell death by mainly inhibiting PERK phosphorylation; additionally, C. asiatica also suppressed the expression levels of GRP94 and BiP. In Y-maze test, oral administration of araliadiol (10 mg/kg/day) for 7 days ameliorated the arm alternation ratio in mice with scopolamine-induced cognitive impairment. These results suggest that C. asiatica and its active component, araliadiol, have neuroprotective effects, which may prevent cognitive dysfunction.

New iridal-type triterpenoid analogues with 6/5/6-fused carbon skeleton from the rhizomes of Belamcanda chinensis.

Five new iridal-type triterpenoid derivatives with 6/5/6 tricyclic ring skeleton (1-5) were obtained from the rhizomes of Belamcanda chinensis. Their structures were determined on the basis of detailed spectroscopic data and ECD calculation. Compounds 1-5 possessed the same 6/5/6-fused carbon skeleton as Belamchinenin A, which further enriched this kind of iridals. In vitro bioassay, compounds 2 and 3 exhibited 51.95 and 54.52% inhibitory activities, respectively, against Fe2+/cysteine-induced liver microsomal lipid peroxidation at a concentration of 10 µM. A putative biogenetic pathway for compounds 1-5 was proposed.

Bioactive triterpenoids from Solanum torvum fruits with antifungal, resistance modulatory and anti-biofilm formation activities against fluconazole-resistant candida albicans strains.

Vulvovaginal candidiasis (VVC) is the second most common vaginal infection that affects women of reproductive age. Its increased occurrence and associated treatment cost coupled to the rise in resistance of the causative pathogen to current antifungal therapies has necessitated the need for the discovery and development of novel effective antifungal agents for the treatment of the disease. We report in this study the anti-Candida albicans activity of Solanum torvum 70% ethanol fruit extract (STF), fractions and some isolated compounds against four (4) fluconazole-resistant strains of C. albicans. We further report on the effect of the isolated compounds on the antifungal activity of fluconazole and voriconazole in the resistant isolates as well as their inhibitory effect on C. albicans biofilm formation. STF was fractionated using n-hexane, chloroform (CHCl3) and ethyl acetate (EtOAc) to obtain four respective major fractions, which were then evaluated for anti-C. albicans activity using the microbroth dilution method. The whole extract and fractions recorded MICs that ranged from 0.25 to 16.00 mg/mL. From the most active fraction, STF- CHCl3 (MIC = 0.25-1.00 mg/mL), four (4) known compounds were isolated as Betulinic acid, 3-oxo-friedelan-20α-oic acid, Sitosterol-3-ß-D-glucopyranoside and Oleanolic acid. The compounds demonstrated considerably higher antifungal activity (0.016 to 0.512 mg/mL) than the extract and fractions and caused a concentration-dependent anti-biofilm formation activity. They also increased the sensitivity of the C. albicans isolates to fluconazole. This is the first report of 3-oxo-friedelan-20α-oic acid in the plant as well as the first report of betulinic acid, sitosterol-3-ß-D-glucopyranoside and oleanolic acid from the fruits of S. torvum. The present study has demonstrated the anti-C. albicans activity of the constituents of S. torvum ethanol fruit extract and also shown that the constituents possess anti-biofilm formation and resistance modulatory activities against fluconazole-resistant clinical C. albicans isolates.

Triterpenoid Saponins from the Cultivar "Green Elf" of Pittosporum tenuifolium.

Four oleanane-type glycosides were isolated from a horticultural cultivar "Green Elf" of the endemic Pittosporum tenuifolium (Pittosporaceae) from New Zealand: three acylated barringtogenol C glycosides from the leaves, with two previously undescribed 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, 3-O-ß-d-galactopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and the known 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C (Eryngioside L). From the roots, the known 3-O-ß-d-glucopyranosyl-(1→2)-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyloleanolic acid (Sandrosaponin X) was identified. Their structures were elucidated by spectroscopic methods including 1D- and 2D-NMR experiments and mass spectrometry (ESI-MS). According to their structural similarities with gymnemic acids, the inhibitory activities on the sweet taste TAS1R2/TAS1R3 receptor of an aqueous ethanolic extract of the leaves and roots, a crude saponin mixture, 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and Eryngioside L were evaluated.

Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats.

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p-AktSer473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1-C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1-C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.

New Polyesterified Ursane Derivatives from Leaves of Maesa membranacea and Their Cytotoxic Activity.

Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1-2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol (1) and 2α,6ß,22α-triacetoxy-urs-12-ene-3α,11α,20ß-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145-IC50 = 35.8 µg/mL, PC3-IC50 = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%.

Green extraction optimization of triterpenoid glycoside-enriched extract from Centella asiatica (L.) Urban using response surface methodology (RSM).

Centella asiatica (L.) Urban extracts are widely used as food, drugs and cosmetics, and the main active compounds are glycosides (madecassoside and asiaticoside) and aglycones (madecassic acid and asiatic acid). Green extraction is an interesting concept that can produce safe and high-quality extracts that use less solvent, time and energy with the environmental friendly. This study investigated the optimum conditions for extracting a triterpenoid glycoside-enriched C. asiatica extract using microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE). Central composite design and response surface methodology (RSM) were used for the experimental design and data analysis. Four-month-old C. asiatica tetraploid plants were selected as the elite raw material containing high amount of triterpenoid glycosides for the extraction experiments, and the triterpenoid content was determined by a validated HPLC method. The results demonstrated that the RSM models and equations were reliable and could predict the optimal conditions to enhance C. asiatica extract yield, glycoside and aglycone amounts. The percent of ethanol was the major factor that had a significant effect on C. asiatica yield and glycoside and aglycone content during MAE and UAE. The maximum triterpenoids content in extract; 7.332 ± 0.386% w/w madecassoside and 4.560 ± 0.153% w/w asiaticoside 0.357 ± 0.013% w/w madecassic acid and 0.209 ± 0.025% w/w asiatic acid were obtained by MAE with 80% ethanol at 100 watts for 7.5 min, whereas the optimal conditions for highest total triterpenoids extraction from dry plant was UAE with 80% ethanol, temperature 48 °C, 50 min enhanced 2.262 ± 0.046% w/w madecassoside, 1.325 ± 0.062% w/w asiaticoside, 0.082 ± 0.009% w/w madecassic acid and 0.052 ± 0.007% w/w asiatic acid as secondary outcome. Moreover, it was found that MAE and UAE consumed energy 59 and 54%, respectively, lower than that of the conventional method, maceration, in term of kilowatt-hour per gram of total triterpenoids. These optimized green conditions could be recommended for C. asiatica extraction for triterpenoid glycoside-enriched extracts production for the pharmaceutical or cosmeceutical industries and triterpenoids quantitative analysis in raw materials.

Ursane-Type Triterpenes, Phenolics and Phenolic Derivatives from Globimetula braunii Leaf.

Globimetula braunii is a hemi-parasitic plant used in African ethnomedicine for the management of microbial infections, rheumatic pain and tumors amongst others. We report the isolation and characterization of eight compounds with their antioxidant and antimicrobial activities. The air-dried powdered leaf was macerated in EtOH/H20 (4:1). The extract was solvent-partitioned into n-hexane, EtOAc, n-BuOH and aqueous fractions. The fractions were screened for their antioxidant properties, using DPPH, FRAP, TAC and FIC assays. Antimicrobial analysis was performed using the micro-broth dilution method. The active EtOAc fraction was purified for its putative compounds on a repeated silica gel column chromatography monitored with TLC-bioautography. The isolated compounds were characterized using spectroscopic methods of UV, FT-IR, NMR and MS. Eight compounds (1-8) were isolated and characterized as 13,27-cycloursane (1), phyllanthone (2), globraunone (3), three phenolics: methyl 3,5-dihydroxy-4-methoxybenzoate (4), methyl 3-methyl-4-hydroxybenzoate (5) and guaiacol (6), as well as two phenol derivatives: 4-formaldehyde phenone (7) and 6-methoxy-2H-inden-5-ol (8). The study identified 4 and 6 as natural antioxidant compounds with potential as antimicrobial agents.

Iridal-Type Triterpenoids Displaying Human Neutrophil Elastase Inhibition and Anti-Inflammatory Effects from Belamcanda chinensis.

The aim of this study is to explore anti-inflammatory phytochemicals from B. chinensis based on the inhibition of pro-inflammatory enzyme, human neutrophil elastase (HNE) and anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage. Three stereoisomers of iridal-type triterpenoids (1-3) were isolated from the roots of B. chinensis and their stereochemistries were completely identified by NOESY spectra. These compounds were confirmed as reversible noncompetitive inhibitors against HNE with IC50 values of 6.8-27.0 µM. The binding affinity experiment proved that iridal-type triterpenoids had only a single binding site to the HNE enzyme. Among them, isoiridogermanal (1) and iridobelamal A (2) displayed significant anti-inflammatory effects by suppressing the expressions of pro-inflammatory cytokines, such as iNOS, IL-1ß, and TNF-α through the NF-κB pathway in LPS-stimulated RAW264.7 cells. This is the first report that iridal-type triterpenoids are considered responsible phytochemicals for anti-inflammatory effects of B. chinensis.

Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-ß-boswellic acid isolated from Boswellia serrata.

Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 µg/mL and 26.5 ± 4.5 µg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-ß-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 µg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.

Investigation of HIV-1 Viral Protein R Inhibitory Activities of Twelve Thai Medicinal Plants and Their Commercially Available Major Constituents.

Viral protein R (Vpr) is an accessory protein in Human immunodeficiency virus-1 (HIV-1) and has been suggested as an attractive target for HIV disease treatment. Investigations of the ethanolic extracts of twelve Thai herbs revealed that the extracts of the Punica granatum fruits, the Centella asiatica aerials, the Citrus hystrix fruit peels, the Caesalpinia sappan heartwoods, the Piper betel leaves, the Alpinia galangal rhizomes, the Senna tora seeds, the Zingiber cassumunar rhizomes, the Rhinacanthus nasutus leaves, and the Plumbago indica roots exhibited the anti-Vpr activity in HeLa cells harboring the TREx plasmid encoding full-length Vpr (TREx-HeLa-Vpr cells). Moreover, the investigation of the selected main constituents in Punica granatum, Centella asiatica, A. galangal, and Caesalpinia sappan indicated that punicalagin, asiaticoside, ellagic acid, madecassic acid, madecassoside, zingerone, brazilin, and asiatic acid possessed anti-Vpr activities at the 10 µM concentration. Among the tested extracts and compounds, the extracts from Centella asiatica and Citrus hystrix and the compounds, punicalagin and asiaticoside, showed the most potent anti-Vpr activities without any cytotoxicity, respectively.

Extraction, isolation and structural characterization of two triterpenoid glycosides from the fruits of Ficusbengalensis.

Ficus bengalensis (F. bengalensis) is a popular medicinal plant species used extensively in the Ayurveda treatment as hypoglycemic, diuretic, tonic, rheumatism, astringent, and inflammation. The goal of this study is to separate and characterize - compounds from fruits of the selected F. bengalensis. The dried fruits coarse power was defatted with non-polar solvent petroleum ether and then systematically extracted with ethanol by using maceration method for 3 days. The ethanol was evaporated and the prepared extract was separated by several chromatographic methods. After separation, the ethanol extract of F. bengalensis afforded nine compounds including two new triterpenoid glycoside derivatives Compound 1: Bengalensursenyl diglycoside and Compound 2: Ficusbengursenyl diglycoside and other minor known phytochemicals. The chemical structures of these separated phytochemicals were elucidated based on spectroscopic analysis and minor chemical transformations. This paper reports isolation and structure elucidation of compounds 1 and 2. In conclusion, the isolated Compound 1 and Compound 2 could be further investigated for any pharmacological activities. This is the first report in our laboratory on isolation of Compound 1 and Compound 2 from the fruits of F. bengalensis.