Densitometric method for assessment of six specialized metabolites in four Sida sp. and its congener Abutilon indicum: Targeted metabolomics, greenness assessment, and chemometrics analysis.

Sida is one of the most diverse genera, with about 200 species distributed in tropical and subtropical regions of the world. Among 18 species distributed in India, Sida acuta, Sida cordifolia, Sida rhombifolia, and Sida cordata are used in traditional medicines along with its possible adulterant Abutilon indicum for several therapeutic uses. The non-availability of marker-based validated methods for the identification and classification of these species leads to adulteration. Indoloquinoline and quinazoline are the major bioactive alkaloids distributed in Sida spp. First time, a simple, economical and high throughput method was developed and validated for the simultaneous determination of 20-hydroxyecdysone (1), vasicine (2), vasicinone (3), cryptolepine (4), quindolinone (5), and cryptolepinone (6) using HPTLC-UV densitometry. The method was validated to meet globally accepted ICH guidelines. The method was sensitive with LOD and LOQ ranging from 0.38-0.63 and 1.57-2.12 µg/band. The samples were spiked at 3 different concentrations, the recovery values were 93.49-98.88%. In addition, the greenness index of the HPTLC method was estimated using four different greenness assessment techniques. Targeted HPTLC analysis indicated the distribution of specialized metabolites in Sida spp. and A. indicum. However, the occurrence of cryptolepine in A. indicum was not reported in the literature, so this was further confirmed by liquid chromatographic studies of the samples from different locations. The chromatographic data was statistically evaluated by principal component analysis (PCA) and hierarchical clustering (HCA). HPTLC-based targeted metabolite quantitation explains the adulteration/substitution in Sida raw material and derived herbal preparations.

Anti-inflammatory quinoline-4(1H)-one derivatives from the aerial parts of Waltheria indica linn.

Eight previously undescribed quinoline-4(1H)-one derivatives (1-8) and five known analogues (9-13) were isolated from the 95% aqueous extract of the aerial parts of Waltheria indica Linn. Their chemical structures were determined by analyzing 1D NMR, 2D NMR and HRESIMS data comprehensively. Compounds 1-8 possess diverse side chains at C-5 of quinoline-4(1H)-one or tetrahydroquinolin-4(1H)-one skeleton. The absolute configurations were assigned via comparison of the experimental and calculated ECD spectra, and analysis of the ECD data of the in situ formed [Rh2(OCOCF3)4] complex. Additionally, all 13 isolated compounds were evaluated for their anti-inflammatory activities by measuring the inhibitory effects of nitric oxide (NO) production in lipopolysaccharide-induced BV-2 cells. Compounds 2, 5 and 11 showed moderate inhibition toward NO production with IC50 values of 40.41 ± 1.01, 60.09 ± 1.23 and 55.38 ± 0.52 µM, respectively.

α-Glucosidase inhibition of sesquiterpenoids from the heartwood of Mansonia gagei.

Nine undescribed sesquiterpenoids, along with ten known compounds, were isolated from the ethyl acetate extract of Mansonia gagei heartwood. Their structures were determined by spectroscopic data analysis (FTIR, 1D, 2D NMR, and HRESIMS), and their absolute configurations were established by ECD calculation. The isolated compounds were evaluated for their inhibitory effect against α-glucosidase from yeast. The results showed that mansonone U, mansonialactam, heliclactone and mansonone S exhibited exceptionally potent activities when compared to the positive control, acarbose, with IC50 values of 12.38 ± 0.71, 0.20 ± 0.05, 13.12 ± 2.85, and 12.05 ± 1.91 µM, respectively. Among them, mansonialactam possessed the most potent inhibitory activity against yeast α-glucosidase, and it showed an uncompetitive inhibition mode.

Total Synthesis of Waltherione A, a Quinolone Alkaloid Fused with Oxabicyclo[3.2.1]octane.

Waltherione A (1), a unique quinolone alkaloid fused with oxabicyclo[3.2.1]octane, was isolated originally from Waltheria douradinha and recently by us from a methanol extract of Melochia umbellata along with the related 3,4-dimethoxyquinoline paliasanines A-E. Compound 1 showed selective cytotoxicity against A549 and MCF-7 cell lines. Its interesting structural and biological features prompted several attempts at total synthesis and clarification of the absolute configuration, although none were successful to date. Now, we have accomplished the first total synthesis of 1 starting from commercially available benzosuberone in 21 steps as well as elucidated its absolute configuration.

Antimycobacterial Activity of Sida hermaphrodita (L.) Rusby (Malvaceae) Seed Extract.

The current prevalence of such lifestyle diseases as mycobacteriosis and tuberculosis is a result of the growing resistance of microorganisms to the available antibiotics and their significant toxicity. Therefore, plants can successfully become a source of new therapeutic agents. The aim of this study was to investigate the effect of protein extract from Sida hermaphrodita seeds on the morphology, structure, and viability of Mycobacterium smegmatis and to carry out proteomic characterization of the protein extract. The analyses were carried out using fluorescence and transmission microscopy, atomic force microscopy, and spectroscopy. The proteomic studies were performed using liquid chromatography coupled to tandem mass spectrometry. The studies showed that the seed extract applied at concentrations of 50-150 µg/mL exerted a statistically significant effect on M. smegmatis cells, that is, a reduction of the viability of the bacteria and induction of changes in the structure of the mycobacterial cell wall. Additionally, the SEM analysis confirmed that the extract did not have a cytotoxic or cytopathic effect on fibroblast cells. The proteomic analysis revealed the presence of structural, storage, and enzymatic proteins and peptides in the extract, which are typical for seeds. Proteins and peptides with antimicrobial activity identified as vicillins and lipid-transporting proteins were also determined in the protein profile of the extract.

Anti-inflammatory Quinoline Alkaloids from the Roots of Waltheria indica.

Sixteen new quinoline alkaloids (1a-7, 8a, 9, 10, 13-15, 17, and 21) and 10 known analogs (8b, 11, 12, 16, 18-20, and 22-24), along with three known cyclopeptide alkaloids (25-27), were isolated from the roots of Waltheria indica. The structures of the new compounds were elucidated by detailed NMR and circular dichroism with computational support and mass spectrometry data interpretation. Anti-inflammatory potential of isolates was evaluated based on inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity with cell culture models. In the absence of cell growth inhibition, compounds 6, 8a, 9-11, 13, 21, and 24 reduced TNF-α-induced NF-κB activity with IC50 values ranging from 7.1 to 12.1 µM, comparable to the positive control (BAY 11-7082, IC50 = 9.7 µM). Compounds 6, 8a, 8b, and 11 showed significant NO-inhibitory activity with IC50 values ranging from 11.0 to 12.8 µM, being more active than the positive control (l-NMMA, IC50 = 22.7 µM). Structure-activity relationships indicated that NO inhibitory activity was significantly affected by C-8 substitution. Inhibition of LPS-induced nitric oxide synthase (iNOS) by 8b [(5S)-waltherione M, IC50 11.7 ± 0.8 µM] correlated with inhibition of iNOS mRNA expression. The biological potential of W. indica metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.

Gagones A-F: Six prenylated chalcones from the heartwood of Mansonia gagei.

Six undescribed prenylated chalcones gagones A-F were isolated from the acetone fraction of Mansonia gagei heartwood. Their structures were unambiguously established based on spectroscopic analysis (HRESIMS, 1D and 2D NMR), as well as comparison to literature data. Their absolute configurations were elucidated using DP4 and electronic circular dichroism calculations. Isolated compounds were evaluated for their inhibitory activity against α-glucosidase and DPPH assay. All of the tested compounds exhibited better activity than that of acarbose (IC50 93.6 ± 0.5 µM). Among them, gagone D exhibited the highest α-glucosidase inhibitory with the IC50 value of 3.6 ± 0.4 µM. For antioxidant activity, gagones A-C, and E showed more active than that of ascorbic acid (IC50 30.2 ± 0.5 µM) with the IC50 values of 13.2 ± 0.7, 20.1 ± 0.4, 19.3 ± 0.5 and 12.8 ± 0.2 µM, respectively.

Evidence for the Involvement of Cytokines Modulation and Prokinetic Properties in Gastric Ulcer Healing Effects of Helicteres sacarolha A. St.-Hil. A. Juss.

Preparations of Helicteres sacarolha (Malvaceae) leaves and roots are used in the form of decoction, infusion or maceration, to treat gastrointestinal disturbances, among others. Studies supporting some of its ethnomedicinal uses are still incipient. The present study aimed to investigate it potential effect on chronic ulcer, ulcerative colitis and possible prokinetic activities as part of its mechanism of action. The powdered leaves of Helicteres sacarolha (HEHs) was prepared by maceration in 70 % hydroethanolic solution. Its qualitative phytochemical constituents were investigated by direct flow injection analysis coupled to atmospheric pressure chemical ionization ion trap tandem mass spectrometry (FIA-APCI-IT-MSn ). The gastric ulcer healing effect was evaluated in acetic acid induced chronic ulcer in mice and the lesions were evaluated, including analysis of blood plasma cytokine levels. The prokinetic properties (gastric emptying and intestinal transit) were carried out in mice. Potential anti-ulcerative colitis activity was evaluated in rats using 2,4,6-trinitrobenzenesulfonic acid (5 % TNBS) -induced colitis. All animal experiments were carried out at the doses of 20, 50 and 250 mg/kg (p.o.). Eight compounds were putatively identified, specifically lariciresinol, and its derivatives, kaempferol derivatives and Tricin-O-Glc. The extract promoted increased gastric ulcer healing at all doses tested. Modulation of the cytokines involved inhibition of some key pro-inflammatory cytokines with maximum effect on IL-1ß (70 %, 50 mg/kg, p<0.05), TNF-α (79 %, 20 mg/kg, p<0.01), and in the anti-inflammatory cytokines, namely IL-10 (57 %, 50 mg/kg, p<0.05) and IL-17 (79 %, only at 50 mg/kg, p<0.05). Histological findings demonstrated a mitigated inflammatory activity, and tissues undergoing regeneration. HEHs treatment caused delayed gastric emptying, and increased intestinal transit, but had no effect in the experimentally induced ulcerative colitis. We report for the first time putatively the presence of Lariciresinol and tricin derivatives from the hydroethanolic leaves extract of H. sacarolha. Its possible mechanism of actions of gastric ulcer healing involves cytokines modulation, mitigation of inflammatory response and tissue regeneration and provoked opposing effect in the gastrointestinal system. The present study demonstrates the therapeutic potential of H. sacarolha leaves used in Brazilian ethnomedicine in the treatment of chronic gastric ulcer.

Microgrewiapine C: Asymmetric Synthesis, Spectroscopic Data, and Configuration Assignment.

The first asymmetric synthesis of microgrewiapine C, a piperidine alkaloid isolated from Microcos paniculata, is reported. This synthesis prompted correction of the 1H and 13C NMR data for the natural sample of the alkaloid, which was achieved by reanalysis of the original spectra. The corrected data for the natural product were found to be identical to those of the synthetic sample prepared herein, thus confirming the structural and relative configurational assignment of microgrewiapine C. Although comparison of specific rotation values indicates that the (1R,2S,3S,6S) absolute configuration should be assigned to the alkaloid, consideration of potential common biosynthetic origins of microgrewiapine C and congeners suggests that further phytochemical investigations are warranted.

Coumarinolignans with Reactive Oxygen Species (ROS) and NF-κB Inhibitory Activities from the Roots of Waltheria indica.

Seven new coumarinolignans, walthindicins A-F (1a, 1b, 2-5, 7), along with five known analogs (6, 8-11), were isolated from the roots of Waltheria indica. The structures of the new compounds are determined by detailed nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. Compounds were tested for their antioxidant activity in Human Cervical Cancer cells (HeLa cells). Compounds 1a and 6 showed higher reactive oxygen species (ROS) inhibitory activity at 20 µg/mL when compared with other natural compound-based antioxidants such as ascorbic acid. Considering the role of ROS in nuclear-factor kappa B (NF-κB) activation, compounds 1a and 6 were evaluated for NF-κB inhibitory activity and showed a concentration-dependent inhibition in Human Embryonic Kidney 293 cells (Luc-HEK-293).

Avaliação da citotoxicidade in vitro e genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke (Malvaceae / Evaluation of in vitro cytotoxicity and ex-vivo genotoxicity in compounds from Pavonia glazioviana Gürke(Malvaceae)

Introdução: as terapias alternativas que utilizam plantas medicinais e fitoterápicos são bastante comuns no Brasil. Dentre várias espécies vegetais brasileiras utilizadas em terapias destacam-se as espécies da família Malvaceae. Objetivos: o presente estudo teve como objetivo avaliar a citotoxicidade in vitro e a genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke espécie brasileira pertencente à família Malvaceae. Metodologia: métodos in vitro foram utilizados para verificar o potencial citotóxico por meio de ensaios hemolíticos e anti-hemolíticos e da análise genotóxica ex-vivo. O Extrato Etanólico Bruto (EEB) e Fração Clorofórmico (FC) foram obtidos na amostra vegetal utilizada neste estudo. Resultados: os produtos EEB-Pg e FC-Pg apresentaram baixo efeito citotóxico apenas nas concentrações de 50 e 100 µg / mL. As amostras expostas às concentrações de 500 e 1000 µg / mL apresentaram índice hemolítico alto a moderado com lise superior a 60%. Foi descrito efeito anti-hemolítico moderado em todas as amostras tratadas com 500 e 1000 µg / mL, com hemólise < 60%. Além disso, os compostos mostraram baixo efeito genotóxico ex-vivo, com um índice geral de células normais superior a 84% em todas as concentrações. Conclusões: os resultados sugerem um baixo perfil tóxico dos compostos obtidos da espécie Pavonia glazioviana, indicando limites seguros para o uso desses produtos naturais.

Introduction: alternative therapies using medicinal plants and herbal medicines are quite common in Brazil. Among several Brazilian plant species used in therapies, the species of the Malvaceae family stand out. Objetctives: the present study aimed to evaluate the in vitro cytotoxicity and ex-vivo genotoxicity in compounds of the Brazilian Pavonia glazioviana Gürke belonging to the Malvaceae family. Methodology: in vitro methods were used to verify the cytotoxic potential through hemolytic and antihemolytic assays and the ex-vivo genotoxic analysis. The Crude Etanolic Extract (CEE) and Cloroformic Fraction (CF) was obtained in vegetal sample used on this study. Results: the CEE-Pg and CF-Pg products only showed a low cytotoxic effect at the concentrations of 50 and 100 µg/mL. The exposure to the concentrations of 500 and 1000 µg/mL showed a high to moderate hemolytic index with lysis higher than 60%. A moderate anti-hemolytic effect was described in all samples treated with 500 and 1000 µg/mL, with hemolysis <60%. In addition, the compounds showed low ex-vivo genotoxic effect with a general index of normal cells greater than 84% at all concentrations. Conclusion: the results suggest a low toxic profile of the compounds obtained from the Pavonia glazioviana Gürke species belonging to the Malvaceae family, indicating safe limits for the use of these natural products.

Abubidentin A, New Oleanane-type Triterpene Ester from Abutilon bidentatum and its antioxidant, cholinesterase and antimicrobial activities.

Background: This work describes the phytochemical and biological investigation of aerial parts of Abutilon bidentatum Hochst. Of Saudi origin. Methodology: Petroleum ether fraction of ethanolic extract A. bidentatum was fractionated on a silica gel column and further purified with different chromatographic procedures for the isolation of chemical compounds. The chemical structures of all the pure isolated compounds were elucidated by the interpretation of their spectral data using IR, UV, 1H, 13C NMR, and MS spectroscopy and chemical methods (alkaline hydrolysis) as well as comparison with data reported in the literature. The extract and isolated compounds were evaluated for antioxidant, cholinesterase inhibitory, and antimicrobial activities. Results: A new oleanane-type triterpene ester, namely abubidentin A (3) (α, 3ß, 30-trihydroxy-29-carboxy-olean-9(11), 12-diene-3-dotriacontanoate), along with two known compounds: 2-hydroxydocosanoic acid (1) and stigmasta-22-ene-3-ß-ol (2) were isolated from the aerial parts of Abutilon bidentatum Hochst. (Malvaceae). Concerning the biological potential, the abubidentinA displayed antioxidant, cholinesterase inhibitory and antimicrobial activities. AbubidentinA possessed strong antioxidant activity against DPPH and ABTS+ radical scavenging assays. This new triterpene exhibited high inhibition against acetylcholinesterase (IC50 38.13 ± 0.07 µgmL-1) and butyrylcholinesterase (IC50 32.68 ± 0.37 µgmL-1). Abubidentin A displayed promising antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (125-150 µgmL-1). Conclusion: These findings suggest A. bidentatum can contribute as a source of new biologically active compounds, especially antioxidants and antimicrobial agents.

Extracts of Sida cordifolia contain polysaccharides possessing immunomodulatory activity and rosmarinic acid compounds with antibacterial activity.

BACKGROUND: The overuse of antibiotics has led to increased antimicrobial resistance, but plant-derived biological response modifiers represent a potential alternative to these drugs. This investigation examined the immunomodulatory and antibacterial activities of Sida cordifolia (used in ethnomedicinal systems to treat infectious disease). METHODS: Successive extractions were performed from the roots of these plants in hexane, chloroform, methanol and water. Immunomodulatory activity was determined in a series of experiments measuring the responses of splenocytes, macrophages and an in vivo model of innate immunity (Galleria mellonella). Antibacterial activity was assessed by determining minimum inhibitory/bactericidal concentrations (MIC/MBCs) for various Gram-positive and Gram-negative bacterial strains. RESULTS: Immunomodulatory activity was confined to the aqueous extract, and further fractionation and biochemical analysis yielded a highly potent polysaccharide-enriched fraction (SCAF5). SCAF5 is a complex mixture of different polysaccharides with multiple immunomodulatory effects including immune cell proliferation, antibody secretion, phagocytosis, nitric oxide production, and increased expression of pro-inflammatory cytokines. Furthermore, Galleria mellonella pre-treated with SCAF5 produced more haemocytes and were more resistant (P < 0.001) to infection with methicillin-resistant Staphylococcus aureus (MRSA) with a 98% reduction in bacterial load in pre-treated larvae compared to the negative control. The antibacterial activity of Sida cordifolia was confined to the methanolic fraction. Extensive fractionation identified two compounds, rosmarinic acid and its 4-O-ß-d-glucoside derivative, which had potent activity against Gram-positive antibiotic-resistant bacteria, including MRSA. CONCLUSIONS: Sida cordifolia counters bacterial infections through a dual mechanism, and immunomodulatory polysaccharides from this plant should be isolated and characterised to realise their potential as anti-infective agents. Such properties could be developed as an antibiotic alternative (1) in the clinic and (2) alternative growth promoter for the agri-food industry.

First report of compounds from an Ancistrocarpus species: Triterpenoids from A. densispinosus Oliv. (Malvaceae).

The stem bark of Ancistrocarpus densispinosus Oliv. exhibited triterpenoids, including the rare fernane-type, fern-9(11)-ene-2α,3ß-diol (1) a possible chemotaxonomically distinct biomolecule for the genus. Other triterpenoids that were isolated from this plant include the ursane-type ursolic acid (2) and corosolic acid (3), friedelane-type friedelin (4) and canophyllol (5), lupane-type lupeol (6), betulin (7), betulinic acid (8) and hennadiol (9), oleanoic acid (10), maslinic acid (11) and taraxerol (12) and three sterols. This is the first report of the chemistry of a plant of the Ancistrocarpus. The structures of the compounds were elucidated based on their NMR, IR and MS techniques and by comparisons of their experimental data with those reported. The twelve triterpenoids 1-12 were found to be inactive against five bacterial strains Escherichia coli, Bacillus subtilis, Pseudomonas agarici, Micrococcus luteus and Staphylococcus warneri; inactive against KB-3-1 cervix carcinoma cancer cell line and inactive as antioxidants in the DPPH assay.

Chemical constituents of two Cameroonian medicinal plants: Sida rhombifolia L. and Sida acuta Burm. f. (Malvaceae) and their antiplasmodial activity.

An extensive phytochemical investigation of the EtOH/H2O (7:3) extracts of Sida rhombifolia L. and Sida acuta Burm. f., yielded a previously undescribed ceramide named rhombifoliamide (1) and a xylitol dimer (2), naturally isolated here for the first time, as well as the thirteen known compounds viz, oleanolic acid (3), ß-amyrin glucoside (4), ursolic acid (5), ß-sitosterol glucoside (6), tiliroside (7), 1,6-dihydroxyxanthone (8), a mixture of stigmasterol (9) and ß-sitosterol (10), cryptolepine (11), 20-Hydroxyecdysone (12), (E)-suberenol (13), thamnosmonin (14) and xanthyletin (15). Their structures were elucidated by the analyses of their spectroscopic and spectrometric data (1 D and 2 D NMR, and HRESI-MS) and by comparison with the previously reported data. The crude extracts, fractions, and some isolated compounds were tested against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains. All the tested samples demonstrated moderate and/or significant activities against 3D7 (IC50 values: 0.18-20.11 µg/mL) and Dd2 (IC50 values: 0.74-63.09 µg/mL).[Formula: see text].

Glyphaeaside C- enriched extract of Glyphaea brevis restored the antioxidant and reproductive integrity of 1,4-Dinitrobenzene-intoxicated rats.

This study assessed the fertility potential of methanol leaf extract of Glyphaea brevis (MGB) in rats exposed to 1,4-Dinitrobenzene (DNB), an environmental reprotoxicant. Male Wistar rats were orally exposed to 50 mg/kg DNB and administered 750 mg/kg MGB, 1500 mg/kg MGB or 300 mg/kg vitamin E for 21 days after 48 h of DNB exposure. Determination of serum reproductive hormone levels by enzyme-linked immunosorbent assays, evaluation of hematologic profile, computer-assisted sperm analyses (CASA) of sperm kinematics and morphology, assessment of testicular and spermatozoan antioxidant systems, and histopathological evaluation of reproductive tissues were performed. HPLC-DAD analysis identify Glyphaeaside C as the major component of the extract. In rats toxified with 50 mg/kg DNB, testicular and epididymal weights, serum levels of luteinizing hormone, testosterone and follicle-stimulating hormone, and packed cell volume, haemoglobin concentration, and white blood cell counts were decreased. There was altered sperm kinematics which reflected in increased sperm abnormalities. Treatment with the Glyphaeaside C -enriched MGB counteracted all DNB-induced changes and corrected DNB-induced aberrations in kinematic endpoints. Also, testicular and epididymal antioxidant systems were disrupted and there was damage to tissue histoarchitecture. Furthermore, our molecular docking study revealed that Glyphaeaside-C exhibited high binding affinities to the binding pocket of some free radical generating enzymes. Conclusively, the results indicated that Glyphaeaside C-enriched extract of Glyphaea brevis leaf enhanced the quality of semen and improved the functional capabilities of spermatozoa following exposure of rats to DNB which could translate to enhanced fertility.

Activity-Guided Characterization of COX-2 Inhibitory Compounds in Waltheria indica L. Extracts.

Inflammation is the body's response to infection or tissue injury in order to restore and maintain homeostasis. Prostaglandin E2 (PGE-2) derived from arachidonic acid (AA), via up-regulation of cyclooxygenase-2 (COX-2), is a key mediator of inflammation and can also be induced by several other factors including stress, chromosomal aberration, or environmental factors. Targeting prostaglandin production by inhibiting COX-2 is hence relevant for the successful resolution of inflammation. Waltheria indica L. is a traditional medicinal plant whose extracts have demonstrated COX-2 inhibitory properties. However, the compounds responsible for the activity remained unknown. For the preparation of extracts with effective anti-inflammatory properties, characterization of these substances is vital. In this work, we aimed to address this issue by characterizing the substances responsible for the COX-2 inhibitory activity in the extracts and generating prediction models to quantify the COX-2 inhibitory activity without biological testing. For this purpose, an extract was separated into fractions by means of centrifugal partition chromatography (CPC). The inhibitory potential of the fractions and extracts against the COX-2 enzyme was determined using a fluorometric COX-2 inhibition assay. The characterizations of compounds in the fractions with the highest COX-2 inhibitory activity were conducted by high resolution mass spectrometry (HPLC-MS/MS). It was found that these fractions contain alpha-linolenic acid, linoleic acid and oleic acid, identified and reported for the first time in Waltheria indica leaf extracts. After analyzing their contents in different Waltheria indica extracts, it could be demonstrated that these fatty acids are responsible for up to 41% of the COX-2 inhibition observed with Waltheria indica extract. Additional quantification of secondary metabolites in the extract fractions revealed that substances from the group of steroidal saponins and triterpenoid saponins also contribute to the COX-2 inhibitory activity. Based on the content of compounds contributing to COX-2 inhibition, two mathematical models were successfully developed, both of which had a root mean square error (RMSE) = 1.6% COX-2 inhibitory activity, demonstrating a high correspondence between predicted versus observed values. The results of the predictive models further suggested that the compounds contribute to COX-2 inhibition in the order linoleic acid > alpha linolenic acid > steroidal saponins > triterpenoid saponins. The characterization of substances contributing to COX-2 inhibition in this study enables a more targeted development of extraction processes to obtain Waltheria indica extracts with superior anti-inflammatory properties.

Determination of hemicellulose, cellulose, holocellulose and lignin content using FTIR in Calycophyllum spruceanum (Benth.) K. Schum. and Guazuma crinita Lam.

Capirona (Calycophyllum spruceanum (Benth.) K. Schum.) and Bolaina (Guazuma crinita Lam.) are fast-growing Amazonian trees with increasing demand in timber industry. Therefore, it is necessary to determine the content of cellulose, hemicellulose, holocellulose and lignin in juvenile trees to accelerate forest breeding programs. The aim of this study was to identify chemical differences between apical and basal stem of Capirona and Bolaina to develop models for estimating the chemical composition using Fourier transform infrared (FTIR) spectra. FTIR-ATR spectra were obtained from 150 samples for each species that were 1.8 year-old. The results showed significant differences between the apical and basal stem for each species in terms of cellulose, hemicellulose, holocellulose and lignin content. This variability was useful to build partial least squares (PLS) models from the FTIR spectra and they were evaluated by root mean squared error of predictions (RMSEP) and ratio of performance to deviation (RPD). Lignin content was efficiently predicted in Capirona (RMSEP = 0.48, RPD > 2) and Bolaina (RMSEP = 0.81, RPD > 2). In Capirona, the predictive power of cellulose, hemicellulose and holocellulose models (0.68 < RMSEP < 2.06, 1.60 < RPD < 1.96) were high enough to predict wood chemical composition. In Bolaina, model for cellulose attained an excellent predictive power (RMSEP = 1.82, RPD = 6.14) while models for hemicellulose and holocellulose attained a good predictive power (RPD > 2.0). This study showed that FTIR-ATR together with PLS is a reliable method to determine the wood chemical composition in juvenile trees of Capirona and Bolaina.

Evaluation on Antidiabetic Properties of Medicinal Plants from Myanmar.

OBJECTIVES: To explore the effective and safe medicines for treating diabetes. METHODS: Hydroalcoholic extracts of 130 medicinal plants belonging to 66 families were evaluated using porcine pancreatic lipase (PPL) inhibition and glucose uptake methods together with a literature review. RESULTS: The extracts of 22 species showed the PPL inhibition activity; 18 extracts of 15 species stimulated glucose uptake in 3T3-L1 adipocytes. Among them, Mansonia gagei J.R. Drumm., Mesua ferrea L., and Centella asiatica (L.) Urb. exhibited both activities. The extracts of Caladium lindenii (André) Madison rhizomes and Azadirachta indica A. Juss. leaves presented the utmost lipase inhibitory activity with IC50 of 6.86 ± 0.25 and 11.46 ± 0.06 µg/mL, respectively. The extracts of Coptis teeta Wall. rhizomes and Croton tiglium L. seeds stimulated the maximum glucose uptake. Ten species are reported to have antidiabetic activity for the first time. Flavonoids and triterpenoids are the dominant antidiabetic compounds in selected medicinal plants from Myanmar. CONCLUSIONS: P. zeylanica, L. cubeba, H. crenulate, M. gagei, C. teeta, and M. ferrea are worthy to advance further study according to their strong antidiabetic activities and limited research on effects in in vivo animal studies, unclear chemical constitutes, and safety.

Panchvalkala, a traditional Ayurvedic formulation, exhibits antineoplastic and immunomodulatory activity in cervical cancer cells and C57BL/6 mouse papilloma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Panchvalkala, an Ayurvedic traditional formulation has references in Charak Samhita and Bhavaprakasha Nighantu for the treatment of women with endometriosis-related problems, leucorrhea and vaginal ailments. The formulation comprises of equal ratios of the barks from Ficus glomerata, Ficus virens, Ficus religiosa, Ficus benghalensis, and Thespesia populnea. AIM OF THE STUDY: The present study aimed to evaluate the anticancer and immunomodulatory activity of aqueous extract of Panchvalkala (PVaq) against cervical cancer in vitro and in vivo. MATERIALS AND METHODS: The effect of PVaq on disruption of mitochondrial membrane potential in cervical cancer cell lines, SiHa and HeLa, was studied by using JC1 dye. The expression of generic caspases in the cells after treatment with PVaq was evaluated by ELISA kit. The expression of pRb, p53, E6 and E7 proteins were evaluated by western blotting. Acute oral toxicity and DRF studies were performed in Swiss albino mice by following OECD guidelines 423 and 407, respectively. Tumor retardation study was done in C57BL/6 mouse papilloma model. The mice were divided into six groups: No tumor control (NTC), Tumor control (TC), Cisplatin (Cis) (4 mg/kg b.w.), PVaq 100, 200 mg/kg b.w and combination of PVaq (200 mg/kg b.w.) and Cisplatin (4 mg/kg b.w.). The mice were orally gavaged with PVaq daily for 14 days and cisplatin was given intravenously on every 1st, 5th and 9th day. Hematological and biochemical parameters were studied by using hematology analyzer and kits, respectively. E6 and E7 gene expression in the tumor samples was determined by qPCR. Th1 and Th2 cytokine levels were determined by ELISA. RESULTS: PVaq induced mitochondrial depolarization in SiHa and HeLa, and increased the expression of generic caspases, resulting into apoptosis. PVaq upregulated the expression of tumor suppressor proteins (p53 and pRb) and reduced the expression of viral oncoproteins (E6 and E7). Acute toxicity study displayed non-toxicity of PVaq while DRF study ensured its safe dose for further efficacy studies. PVaq reduced tumor volume and weight in mouse papilloma model and induced immunomodulation in the animals. It increased serum levels of IL-2 (Th1) with a concomitant decrease in IL-10 (Th2) cytokines. The drug did not affect body weight, food consumption and organ histopathology of the animals. CONCLUSIONS: PVaq exhibited anticancer and immunomodulatory activities against cervical cancer cells and female mouse papilloma model.