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Renoprotectors are highly demanded due to environmental nephrotoxic factors. P. longifolia leaves extract alleviating effect was assessed in nephritic-induced rats by whole body shot dose of γ-radiation. Many biomarkers were detected using several assays. Renohistopathological examinations were performed. Moreover, the extract phytoconstituents were identified using spectroscopic analysis. In-vitro anti-inflammatory activity of some compounds was examined using histamine release assay. Post-irradiation treatment with the extract significantly ameliorated all elevated biomarker levels. Creatinine and urea were adjusted, TGF-β/Smad signaling was suppressed causing down-regulation to microRNA-21. Nitric oxide, reactive oxygen species, glutathione and kidney injury molecule-1 were normalized in comparison with the γ-irradiated group. The renohistopathological analysis was consistent with the biochemical study. Phytochemical analysis resulted in the isolation of two diterpenoids (γ-methoxybutenolide clerodane diterpene and 16(R/S)-hydroxycleroda-3,13-dien-16,15-olide-2-one), aporphine alkaloid (anonaine) and flavonol (kaempferol-3-O-rutinoside). The latter two showed moderate anti-histaminic activities. Our results indicated that P. longifolia reduced oxidative stress and nephropathy in rats due to its anti-inflammatory principles.

A new clerodane diterpene, 2β-methoxyhardwickiic acid (1), and four known compounds (2–5) were isolated from the twigs of Monoon membranifolium. The structure of the new compound was determined by extensive spectroscopic methods and ESITOFMS data. The absolute configuration of 1 was established by a comparison of its ECD spectrum and specific rotation with those of related previously reported compounds. All compounds were evaluated for their nitric oxide (NO) production inhibitory activities in RAW264.7 macrophage cells. Compounds 3 and 5 inhibited NO production with IC50 values of 16.1 and 28.9 μM, respectively, which were better than that of standard compound, indomethacin (IC50 = 32.2 μM).

A case of baled alfalfa hay contaminated with multiple weeds induced hepatotoxicity and death in cattle. The hepatotoxic compounds were isolated by bioassay-guided fractionation using a mouse model and identified as salviarin, salvianduline D, rhyacophiline, and 7-hydroxyrhyacophiline. The structure of 7-hydroxyrhyacophiline has not been previously reported. All compounds were found to induce severe acute hepatic necrosis within 24-48 h after a single oral dosage (260-280 mg/kg). The identified diterpenes are known to be found among different Salvia species which led to finding dried plant parts of Salvia reflexa within bales of weedy hay and subsequently a population of S. reflexa was found along the field edges and irrigation ditch banks of the alfalfa hay field. It was thus determined that S. reflexa was responsible for the hepatotoxicity observed in cattle fed the contaminated hay.

The rise of antibiotic resistance presents a significant healthcare challenge and precludes the use of many otherwise valuable antibiotics. One potential solution to this problem is the use of anti...

Salvia semiatrata Zucc. (Lamiaceae) is a species used as a tranquilizer and to relieve pain in folk medicine in Santiago Huauclilla, Oaxaca, Mexico. To evaluate the antinociceptive and anxiolytic-like effects of S. semiatrata extracts and identify a bioactive metabolite. The extracts were obtained by maceration of S. semiatrata aerial parts using solvents in increasing polarity (hexane, ethyl acetate and methanol). A neo-clerodane diterpene was extracted from the ethyl acetate fraction using open column chromatography. Identification of this metabolite was performed by crystallography, 1H NMR, 13C NMR, ATR-IR, ECD, MS and elemental analysis. The antinociceptive activity was explored using the writhing and formalin tests. Whereas, the anxiolytic-like responses were analysed in the open-field, hole-board and plus-maze tests. All the treatments were administered using oral gavage in male CD1 mice and explored 30 min after administration of the individual extracts (300 mg/kg) or the compound 1 (0.1, 1 or 10 mg/kg). All the extracts produced significant reduction in the nociceptive and anxiety-like behaviour compared to mice treated with the vehicle (0.5% tween 80 in saline solution). The spectroscopic analysis corroborated the presence of the neo-clerodane diterpene 7-keto-neoclerodan-3,13-dien-18,19:15,16-diolide (1), as partial responsible of the antinociceptive and anxiolytic-like effects, which produced a dose-dependent response in the writhing test with an ED50=4.15 mg/kg. Discussion and conclusions: These results reinforce the medicinal properties of S. semiatrata in folk medicine, where participation of a neo-clerodane diterpene was evidenced in the inhibitory central nervous system activity of this species.

A clerodane diterpene compound 16-hydroxycleroda-3,13-dien-15,16-olide (CD) is considered a therapeutic agent with pharmacological activities. The present study investigated the mechanisms of CD-induced apoptosis in T24 human bladder cancer cells. CD inhibited cell proliferation in a concentration and time-dependent manner. CD-induced overproduction of reactive oxygen species and reduced mitochondrial membrane potential, associated with reduced expression of Bcl-2 and increased levels of cytosolic cytochrome c, cleaved PARP-1 and caspase-3. In addition, CD treatment led to cell cycle arrest at the G0/G1 phase and inhibited expression of cyclin D1 and cyclin-dependent kinases 2 and 4 and led to increased levels of p21, p27Kip1 and p53. All of these events were accompanied with a reduction of pEGFR, pMEK1/2, pERK1/2, pAkt, pmTOR, pP70S6K1, HIF-1&alpha, c-Myc and VEGF. RNAseq-based analysis revealed that CD-induced cell death was characterised by an increased expression of stress and apoptotic-related genes as well as inhibition of the cell cycle-related genes. In summary, CD induces apoptosis in T24 bladder cancer cells through targeting multiple intracellular signaling pathways as a result of oxidative stress and cell cycle arrest.

Made available in DSpace on 2022-04-29T08:45:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Casearin X (CAS X) is the major clerodane diterpene isolated from the leaves of Casearia sylvestris and has been extensively studied due to its powerful cytotoxic activity at low concentrations. Promising results for in vivo antitumor action have also been described when CAS X was administered intraperitoneally in mice. Conversely, loss of activity was observed when orally administered. Since the advancement of natural products as drug candidates requires satisfactory bioavailability for their pharmacological effect, this work aimed to characterize the CAS X metabolism by employing an in vitro microsomal model for the prediction of preclinical pharmacokinetic data. Rat and human liver microsomes were used to assess species differences. A high-performance liquid chromatography with diode-array detection (HPLC-DAD) method for the quantification of CAS X in microsomes was developed and validated according to European Medicines Agency guidelines. CAS X was demonstrated to be a substrate for carboxylesterases via hydrolysis reaction, with a Michaelis-Menten kinetic profile. The enzyme kinetic parameters were determined, and the intrinsic clearance was 1.7-fold higher in humans than in rats. The hepatic clearance was estimated by in vitro - in vivo extrapolation, resulting in more than 90% of the hepatic blood flow for both species. A qualitative study was also carried out for the metabolite identification by mass spectrometry and indicated the formation of the inactive metabolite CAS X dialdehyde. These findings demonstrate that CAS X is susceptible to first-pass metabolism and is a substrate for specific carboxylesterases expressed in liver, which may contribute to a reduction in antitumor activity when administered by the oral route. Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS) Departamento de Física e Química Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo, Avenida Bandeirantes 3900 Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Do Estado de São Paulo Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo

Yu-Chi Chen,1 Bu-Miin Huang,2 Wei-Chang Lee,3 Yung-Chia Chen3,4 1Department of Urology, E-Da Hospital, Kaohsiung, Taiwan; 2Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Clerodane diterpene, 16-hydroxycleroda-3,13-dien-15,16-olide (CD) isolated from Polyalthia longifolia Benth. & Hook. f. var. pendula was found to be a potential apoptotic inducer in human leukemia, lung cancer, and colon cancer cells. However, the molecular mechanism remains elusive in renal system. Thus, in the present study, the regulatory mechanisms of CD-induced apoptosis in clear cell renal cell carcinoma (ccRCC) cells were investigated. Materials and methods: Cell proliferation was evaluated by colony formation assay and cell cycle analyses. Protein expressions of focal adhesion (FA) related complexes were examined by immunofluorescence staining and Western blot analyses. Cell migration and invasion capabilities of renal cell carcinoma (RCC) cells were determined by wound healing and Transwell assays. Results: CD inhibited cell colony formations, induced cell arrest at G2/M phase, and increased subG1 cell population both in 786-O and A-498. During CD treatment, the “rounded-up” cells were observed. The immune-staining of phosphorylated focal adhesion kinase (pFAK), vinculin, and paxillin displayed disassembly of the FA. Moreover, disruption of actin stress fibers was noted after CD treatment. Consistent with the findings, the expressions of pSrc, pFAK, FAK, vinculin, vimentin, and paxillin were all downregulated by CD. In addition, CD attenuated cell migration and invasion activities accompanied by the reductions of pNF-κB, matrix metalloproteinase (MMP)-2, MMP-9 as well as vascular endothelial growth factor expressions. Conclusion: CD induced cell cycle arrest, FA complex disassembly, and the inactivation of migratory-related signaling pathways to induce apoptosis in ccRCC cells. Keywords: focal adhesion, signaling pathway, Polyalthia longifolia, clerodane diterpene, migration, invasion, renal cell carcinoma, RCC

16α-Hydroxycleroda-3,13(14)Z-dien-15,16-olide (4655K-09 or K-09) is a novel clerodane diterpene lactone reported for its anti-hyperlipidemic efficacy. The objective of the present study was to investigate the probable reversible metabolism of 4655K-09 and evaluate its effects on pharmacokinetic (PK) properties. The PK studies were carried out through intravenous (IV) bolus administration of 4655K-09 and K-9T in mice at a dose of 3, 6 and 12 mg/kg separately. The oral PK study of 4655K-09 was carried out at therapeutic dose of 25 mg/kg. The % AUC of metabolite converted to parent upon its administration % AUCK-09K-9T was found to be 27.28 ± 2.67. The multi-compartmental interconversion model defined reversible and irreversible clearances along with volumes of distribution for parent and metabolite. The results emphasized that hydrolysis of lactone to acid was more efficient than back conversion to parent due to greater extent of irreversible elimination of acid. Further, the role of interconversion in pharmacokinetics of 4655K-09 was evaluated through secondary parameters like conversion coefficients of parent to metabolite ( KK-9TK-09:0.08±0.02 ), metabolite to parent ( KK-09K-9T : 0.019 ± 0.001), exposure enhancement (EE: 1.04 ± 0.006), and recycled fraction (RF: 0.042 ± 0.007), highlighted the minimal role of interconversion. The estimation of oral bioavailability remains unaffected when calculated through considering reversible metabolism. The present model-based interconversion pharmacokinetics of 4655K-09 in mice could be further extended to other species to support its development as anti-hyperlipidemic agent.

The clerodane diterpene family possesses an impressive range of bioactivities and high synthetic challenge due to their unique amalgamation of rings, stereocenters, and oxygenation. Herein, we disclose the first total syntheses of three members, scaparvins B, C, and D, through a route fueled by several chemoselective and carefully orchestrated steps. One such operation is a tailored late-stage C-H functionalization converting a carboxylic acid into a lactone through the oxidation of a tertiary C-H bond under conditions that minimize epoxidation of an alkene. This step, among others, afforded critical functionality to complete the targets. In addition, use of an appropriate chiral catalyst with a Rawal diene renders the sequence enantioselective.

Two new diterpene alkaloids having an N-methyladenine moiety, agelamasines A (1) and B (2), were isolated from an Okinawan marine sponge Agelas sp. The structures of 1 and 2 were elucidated on the basis of spectroscopic analyses. Agelamasine A (1) is the first diterpene alkaloid with a rearranged (4 → 2)-abeo-clerodane skeleton from a marine source, while agelamasine B (2) is a clerodane diterpene alkaloid.

The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting naturally occurring compounds and their derivatives as potential hypolipidemic agents. Some of the interesting natural chemotypes that can control the increased levels of plasma lipids and discussed in this review are compactin, lovastatin, gugglesterone, berberine, lupeol, phytol, polyprenol, aegeline, 4-hydroxyisoleucine, α-asarone, resveratrol, esculeoside A, swertiamarin, rutin, saucerneol B, curcumin and a clerodane diterpene.

Background Dodonaea angustifolia is used in Ethiopian traditional medicine to treat malaria. The objective of this work was to conduct bioassay guided fractionation of the leaves of D. angustifolia using Plasmodium berghei infected mice. Method The antiplasmodial activity of the extracts and pure compounds was evaluated using the standard Peter's four-day suppressive method. The structures of isolated compounds were elucidated using chemi-cal and spectroscopic methods. Results In this study, the ethyl acetate soluble portion of the 80% aqueous MeOH extract of the leaves significantly suppressed parasitaemia in Plasmodium berghei infected mice (80.28% at 150 mg/kg). Three active compounds which exhibited significant percent suppression of parasitaemia by 81% at 40 mg/kg, 80% at 50 mg/kg and 70% at 40 mg/kg, respectively were identified. These are the flavanone pinocembrin (1), the flavanol santin (2) and the clerodane diterpene 2-hydroxy-15,16-epoxyceloda-3,13(16),14-trien-18-oic acid (3). Under similar conditions, chloroquine suppressed parasitaemia by 100% at 25 mg/kg. Chemical study of the ethanol extract of the leaves yielded 5,7,4'-trihydroxy-3,6-dimethoxyflavone (4), ent-16-hydroxy-labdan-3α,8β-dihydroxy,13(14)-en-15,16-olide (5) and 5,6,7-trihydroxy-3,4'-dimethoxyflavone (6). Compound 6 has not been reported before as a natural product. Conclusion From the leaves of D. angustifolia, three compounds with significant antiplasmodial activi-ties were isolated and characterized, with pinocembrin as the most active compound.

Two dimeric clerodane diterpene glycosides, namely, bistinospinosides A (1) and B (2), were isolated from the roots of Tinospora sagittata. Their structures were elucidated by extensive spectroscopic data interpretation. The compounds feature an unusual 1,4-epoxycyclohexane ring in their structures and may be biosynthetically constructed via an intermolecular Diels-Alder [4+2] cycloaddition from the corresponding clerodane diterpene. The compounds were evaluated in a nitric oxide inhibitory assay using J774.1 macrophage-like cells.

Systematic analyses of plants that are used in traditional medicine may lead to the discovery of novel cytotoxic secondary metabolites. Diterpene possesses multiple bioactivities; here, epoxy clerodane diterpene (ECD) was isolated from Tinospora cordifolia (Willd.) stem and shown potential antiproliferative effect in MCF-7 human breast cancer cells. The antiproliferative effect of ECD on MCF-7 cells was systematically analyzed by cell and nuclear morphology, alterations in oxidative stress, and the expression of tumor suppressor and mitochondria-mediated apoptosis-related genes. We found that the IC50 value of ECD was 3.2μM at 24h and 2.4μM at 48h. We observed that the cytotoxicity of ECD was specific to MCF-7 cells, whereas ECD was nontoxic to normal Vero and V79 cells. ECD significantly triggered intracellular ROS generation even from the lower doses of 0.6 and 1.2μM; and it is relative to higher dose of 2.4μM. Further, we used 0.6μM, 1.2μM and 2.4μM as experimental doses to analyze the relative dose-dependent effects. Nuclear staining revealed that cells treated with the 2.4μM dose exhibited characteristic apoptotic morphological changes and that 46% of the cells were apoptotic and 4% were necrotic after 48h. ECD significantly increased the expression of mitochondria-dependent apoptotic pathway-related genes after 48h; we observed significantly (p≤0.05) increased expression of CYP1A, GPX, GSK3β and TNF-α and downregulated expression of NF-κB. ECD also increased the expression of tumor suppressor genes such as Cdkn2A, Rb1 and p53. In addition, we observed that ECD treatment significantly (p≤0.001) upregulated the expression of apoptotic genes such as Bax, cas-3, cas-8, cas-9 and p21 and downregulated the expression of BCL-2, mdm2 and PCNA. In conclusion, ECD regulates the expression of Cdkn2A, p53 and mdm2 and induces apoptosis via the mitochondrial pathway in MCF-7 human breast cancer cells.

The discovery of potent cytotoxic isolates from botanicals provides an opportunity to explore this viable tool for cancer chemoprevention. The antileukemic potential of clerodane diterpene from Polyalthia longifolia leaves has already been established. However, in this present study, utilizing chromatographic techniques we report for the first time, the isolation of a rare tetranorditerpene (compound 1) from P. longifolia. The structure of compound 1 was elucidated and confirmed by spectrophotometric data. UPLC-MS analysis was conducted on the methanolic extract, ethyl acetate fraction, and isolated tetranorditerpene showed that the tetranorditerpene is one of the major constituents of the plant with a retention time of 30.78 min. In addition, a methyl ester derivative (compound 2) of the isolated tetranorditerpene was synthesized. Using the CCK-8 assay, we compared the cytotoxic potential of isolated tetranorditerpene (1) and methyl ester derivative (2) with the previously isolated clerodane diterpenes. Our results showed that the methyl ester derivative (2) displayed the highest inhibitory activity against human leukemia HL-60 cells. The isolated tetranorditerpene (1) did not exhibit significant inhibitory effect against HL-60 cells. Morphological examination indicated chromatin condensation and nuclear fragmentation suggesting induction of apoptosis in compound 2 treated HL-60 cells. The methyl esterification of the isolated tetranorditerpene (1) conferred on it a significant level of antileukemic activity suggesting the possibility of a synergistic relationship between pure compound isolation and synthetic reaction in the discovery of new chemopreventive agents.

Made available in DSpace on 2019-10-06T16:34:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-01 Clerodane diterpenes from Casearia sylvestris are antiulcerogenic and anti-inflammatory. The finding that they may undergo acid degradation or hepatic metabolization led to an investigation of their degradation products. Purified clerodane diterpenes (casearins J and O) were subjected to in vitro assays to simulate their oral administration. Resulting derivatives were identified using chromatographic and spectrometric techniques. Nitric oxide synthesis by LPS-stimulated macrophages was assayed to verify whether structural modifications alter the anti-inflammatory activity of diterpenes. Nine compounds (1–9) were identified after acid degradation remaining 5.05% of casearin J. Besides the remaining casearin O (13.1%), eight compounds (10–17) were identified. The dialdehydes from each casearin were the major constituents. S9 rat liver treatment of casearins J and O generated two compounds identical to some of those produced by acid degradation, which remained 36.8% and 36.5% intact, respectively. Both casearins and its derivatives were not cytotoxicity at concentrations lower than 0.312 μg/mL (0.555 μM for casearin J and 0.516 μM for casearin O) and did not inhibit the nitric oxide production in this concentration. Thus, the structural modifications conducted did not alter the activity of casearins and the anti-inflammatory pathway of diterpenes probably is not involved on nitric oxide modulation. São Paulo State University (Unesp) School of Pharmaceutical Sciences Department of Natural Principles and Toxicology University of São Paulo (USP) Faculty of Philosophy Sciences and Letters Department of Chemistry São Paulo State University (Unesp) School of Pharmaceutical Sciences Department of Biological Sciences University of Araraquara Department of Health and Biological Sciences São Paulo State University (Unesp) School of Pharmaceutical Sciences Department of Natural Principles and Toxicology São Paulo State University (Unesp) School of Pharmaceutical Sciences Department of Biological Sciences

Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment, however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

Biotransformation of the antifungal compound 16-oxocleroda-3,13(14)E-dien-15-oic acid (1) isolated from Polyalthia longifolia leaves was achieved by Rhizopus stolonifer in broth medium containing t...

Terpenoids from Salvia species have been identified to possess biological properties as antiprotozoal agents. Here, we evaluated the antiamoebic and antigiardial activities of 14 known clerodane and modified clerodane-type diterpenes isolated from five Mexican Salvia species against Entamoeba histolytica and Giardia lamblia, and analyzed the effects of the functionalities in decalin ring or in the whole clerodane framework to visualize the structural requirements necessary to produce an antiprotozoal activity. Among these, linearolactone was the most active clerodane diterpene against both protozoa with IC50 values of 22.9 μM for E. histolytica and of 28.2 μM in the case of G. lamblia. In this context it may be a lead compound for the development of novel therapeutic agent for the treatment of diarrhea and dysentery. The remaining diterpenes assayed showed moderate to weak activity against both protozoa. These findings give support to the use of Salvia species in the traditional medicine from Mexico for the treatment of diarrhea. Copyright © 2015 John Wiley & Sons, Ltd.

Crispene E, a new clerodane-type diterpene, inhibited STAT3 dimerization in a cell-free fluorescent polarisation assay and was found to have significant toxicity against STAT3-dependent MDA-MB 231 breast cancer cell line and selectively inhibited the expression of STAT3 and STAT3 target genes cyclin D1, Fascin and bcl-2. Molecular docking studies suggest the molecule inhibits STAT3 by interacting with its SH2 domain. The compound has been isolated from Tinospora crispa and characterized using standard spectroscopic techniques.

A new clerodane diterpene derivative named crotonoligaketone was obtained from the stem bark of Croton oligandrum along with eight known compounds including crotonadiol, imbricatadiol, crotonzambefuran B, 7-acetoxytrachiloban-18-oic acid, 3-O-acetylaleuritolic acid, lupeol, b-sitosterol, and stigmasterol. The structures of the isolated compounds were established on the basis of their spectral data and by comparison with those reported in the literature

Nerve growth factor (NGF) and analog reagents to promote the neurite outgrowth of nerve cells against the neuron degeneration are expected to be potentially useful for the medical treatment of Alzheimer's disease. In our focus on the discovery of bioactive diterpenes, we investigated the chemical constituents of the plant Croton yanhuii. This investigation led to the isolation and identification of two novel clerodane diterpenes (1 and 2). Their structures were elucidated on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESIMS and HR-ESIMS) spectroscopic data analyses. Further biological screenings showed that both of the compounds enhanced NGF-mediated neurite outgrowth from PC12 cells.

The phytochemical study of Uruguayan specimens of Allophylus edulis (Sapindaceae) yielded the isolation of various natural products being some of them reported for the first time in this species. Although most of them are ubiquitous in the plant kingdom, some revealed in this study to have anti insect properties. Two sesquiterpenes (6,7-Epoxicaryophyllene and spathulenol), two phytosterols (sitosterone and sitosterol), a pentacyclic triterpene (lupeol) and a clerodane diterpene were isolated. 6,7-Epoxycaryophyllene, lupeol and sitosterol showed to be deterrent against the aphid Myzus persicae and the coleopteran Epilachna paenulata. Moreover, the crude ethanolic extract of twigs of A. edulis showed to be deterrent against both insect species being some of its fractions also active against another aphid, Rhopalosiphum padi. Various active compounds against different insect models have been isolated from the twigs extract of A. edulis. The results evidenced synergic as well as antagonistic effects in the mixture, summed to differential activity against the insects, a desirable attribute when developing botanical pesticides.

Two new neo-clerodane diterpenoids, teucvisins A and B (1, 2), and three new 19-nor-neoclerodane diterpenoids, teucvisins C-E (3-5), together with ten known constituents (6-15) were isolated from the whole plants of Teucrium viscidum. All the isolates were evaluated for their inhibitory activities of lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 macrophages. The results indicated that compounds 11 and 15 showed moderate inhibition with an IC50 value of 21.9 and 22.4 µM, respectively.

The Staphylococcus aureus bacterium, a nosocomial pathogen often causing untreatable and lethal infection in patients, mutated to become resistant to all the first-line drugs. The present study details the potential of clerodane diterpene 16α-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide (CD) isolated from Polyalthia longifolia against methicillin-resistant S. aureus (MRSA) through in vitro and in vivo assays. Minimum inhibitory concentration (MIC) of CD exhibited significant anti-MRSA activity (15.625–31.25 mg/l) against reference strain and seven clinical isolates, while time kill assays at graded MICs indicated 2.78–9.59- and 2.9–6.18-fold reduction in growth of reference strain and clinical isolates of S. aureus, respectively. The combined effect of the CD and 7.5 % NaCl resulted in significant reduction in microbial count within 24 h, indicating the loss of the salt tolerance ability of S. aureus. Further, release of 260-nm absorbing material and flow cytometric analysis revealed an increased uptake of propidium iodide. These assays may indicate the membrane-damaging potential of CD. The molecule CD was found to interact synergistically with clinically used antibiotics (FICI ≤ 0.5) against all clinical isolates. In infected mice, CD significantly (P