Displaying publications 101 - 120 of 121 in total

Abstract:
Sort:
  1. Malahubban M, Alimon AR, Sazili AQ, Fakurazi S, Zakry FA
    Trop Biomed, 2013 Sep;30(3):467-80.
    PMID: 24189677 MyJurnal
    Leaves of Andrographis paniculata and Orthosiphon stamineus were extracted with water, ethanol, methanol and chloroform to assess their potential as antibacterial and antioxidant agents. High performance liquid chromatography analysis showed that the methanolic extracts of A. paniculata and O. stamineus leaves gave the highest amounts of andrographolide and rosmarinic acid, respectively. These leaf extracts exhibited antimicrobial and antioxidant activities and, at the highest concentration tested (200 mg/mL), showed greater inhibitory effects against the Gram positive bacteria Bacillus cereus and Staphylococcus aureus than 10% acetic acid. Andrographis paniculata and O. stamineus methanolic and ethanolic leaf extracts also showed the strongest antioxidant activity as compared with the other extracts tested. The bioactive compounds present in these leaf extracts have the potential to be developed into natural antibacterial and antioxidant agents that may have applications in animal and human health.
    Matched MeSH terms: Diterpenes/analysis
  2. Hassan WRM, Basir R, Ali AH, Embi N, Sidek HM
    Trop Biomed, 2019 Sep 01;36(3):776-791.
    PMID: 33597499
    Malarial pathogenesis involves among others, uncontrolled or excessive cytokine production arising from dysregulated immune responses mounted by the host to eliminate the plasmodial parasite. The ubiquitous serine/threonine kinase, glycogen synthase kinase3β (GSK3β) is a crucial regulator of the balance between pro- and anti-inflammatory cytokine productions in the inflammatory response to pathogenic infections. Andrographolide, a bioactive compound in Andrographis paniculata, displays GSK3- inhibitory effects. A previous study elsewhere has shown that this compound has antimalarial activity but the molecular basis of its action is yet to be elucidated. Here we aimed to study the anti-malarial activity of andrographolide in a murine model of malarial infection to investigate whether its mechanism of action involves cytokine modulation and inhibition of GSK3β. Andrographolide showed strong and selective anti-plasmodial activity (IC50 = 13.70±0.71 µM; SI = 30.43) when tested against cultures of P. falciparum 3D7. Intraperitoneal administration of andrographolide (5 mg/kg body weight (bw)) into P. berghei NK65-infected ICR mice resulted in chemo-suppression of 60.17±2.12%, and significantly (P<0.05) improved median survival time of infected mice compared to nontreated control. In addition, andrographolide treatment significantly (P<0.05) decreased the level of serum pro-inflammatory cytokine, IFN-γ (1.4-fold) whilst the anti-inflammatory cytokines, IL-10 and IL-4 were increased 2.3- and 2.6-fold respectively. Western blot analyses revealed that andrographolide treatment of P. berghei NK65-infected mice resulted in an increased level of phosphorylated GSK3β (Ser9) in liver of infected mice. Andrographolide administration also decreased the levels of phosphorylated NF-κB p65 (Ser536) and phosphorylated Akt (Ser473) in liver of malaria- infected animals. Taken together, our findings demonstrate that the cytokine-modulating effect of andrographolide in experimental malarial infection involves at least in part inhibition of NF-κB activation as a consequence of GSK3β inhibition. Based on its cytokine-modulating effects, andrographolide is thus a plausible candidate for adjunctive therapy in malaria subject to clinical evaluations.
    Matched MeSH terms: Diterpenes/pharmacology*
  3. Phan CS, Kamada T, Kobayashi K, Hamada T, Vairappan CS
    Nat Prod Res, 2018 Jan;32(2):202-207.
    PMID: 28691521 DOI: 10.1080/14786419.2017.1346638
    A new xenicane diterpenoid, 15-deoxy-isoxeniolide-A (1) along with four known compounds 9-deoxy-isoxeniolide-A (2), isoxeniolide-A (3), xeniolide-A (4) and coraxeniolide-B (5) were isolated from the Bornean soft coral Xenia sp. The structures of these metabolites were elucidated on the basis of spectral analysis, NMR and HRESIMS. Compound 5 showed cytotoxic activity against ATL cell line, S1T.
    Matched MeSH terms: Diterpenes/chemistry*
  4. Abdullah NH, Ismail S
    Molecules, 2018 Oct 19;23(10).
    PMID: 30347696 DOI: 10.3390/molecules23102696
    The co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory effect of several herbal constituents on one of the most important UGT isoforms, UGT2B7, in human liver microsomes (HLM) and rat liver microsomes (RLM) was investigated. Zidovudine (ZDV) was used as the probe substrate to determine UGT2B7 activity. The intrinsic clearance (Vmax/Km) of ZDV in HLM is 1.65 µL/mg/min which is ten times greater than in RLM, which is 0.16 µL/mg/min. Andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone inhibited ZDV glucuronidation in HLM with IC50 values of 6.18 ± 1.27, 18.56 ± 8.62, 8.11 ± 4.48 and 4.57 ± 0.23 µM, respectively, hence, herb-drug interactions are possible if andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone are taken together with drugs that are highly metabolized by UGT2B7. Meanwhile, only mitragynine and zerumbone inhibited ZDV glucuronidation in RLM with IC50 values of 51.20 ± 5.95 μM and 8.14 ± 2.12 µM, respectively, indicating a difference between the human and rat microsomal model so caution must be exercised when extrapolating inhibitory metabolic data from rats to humans.
    Matched MeSH terms: Diterpenes/administration & dosage
  5. Sulaiman I, Tan K, Mohtarrudin N, Lim JCW, Stanslas J
    Pulm Pharmacol Ther, 2018 12;53:39-51.
    PMID: 30244166 DOI: 10.1016/j.pupt.2018.09.008
    Toluene diisocyanate (TDI) is a major cause of chemical-induced occupational asthma, which contributes about 15% of global asthma burden. Resistance and compounded side effects associated with the use of corticosteroid in asthma necessitate the search for alternative drugs. Andrographolide (AGP), a naturally occurring diterpene lactone is known to exhibit various bioactivities. Its ability to ameliorate cardinal features of allergic asthma was previously suggested in an eosinophilic asthma endotype. However, its potential antiasthma activity and mechanism of action in a neutrophilic occupational asthma model, as well as its effect on epithelial dysfunction remain unknown. BALB/c mice were dermally sensitised with 0.3% TDI or acetone olive oil (AOO) vehicle on day 1 and 8, followed by 0.1% TDI intranasal challenge on days 15, 18 and 21. Endpoints were evaluated via bronchoalveolar lavage fluid (BALF) cell analysis, 2',7'-dichlorofluorescein diacetate (DCFDA) assays, immunoblotting, immunohistochemistry and methacholine challenge test. Decreases in total and differential leukocyte counts of BALF were recorded in AGP-treated animals. The compound dose-dependently reduced intracellular de-esterification of DCFDA, thus suggesting AGP's potential to inhibit intracellular reactive oxygen species (ROS). Mechanistically, the treatment prevented TDI-induced aberrant E-cadherin distribution and restored airway epithelial β-catenin at cell to cell contact site. Furthermore, AGP ameliorated TDI induced pulmonary collagen deposition. In addition, the treatment significantly upregulated pulmonary HO-1, Nrf2 and phospho-p38 levels. Airway hyperresponsiveness was markedly suppressed among AGP-treated animals. Collectively, these findings suggest AGP's protective function against TDI-induced airway epithelial barrier dysfunction and oxidative lung damage possibly through the upregulation of adherence junction proteins and the activation of p38/Nrf2 signalling. This study elucidates the therapeutic potential of AGP in the control and management of chemical-induced allergic asthma. To the best of our knowledge, the potential anti-asthma activity of AGP in TDI-induced occupational asthma has not been reported previously.
    Matched MeSH terms: Diterpenes/pharmacology*
  6. Wong CC, Sagineedu SR, Sumon SH, Sidik SM, Phillips R, Lajis NH, et al.
    Environ Toxicol Pharmacol, 2014 Sep;38(2):489-501.
    PMID: 25168151 DOI: 10.1016/j.etap.2014.07.016
    Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.
    Matched MeSH terms: Diterpenes/chemical synthesis; Diterpenes/pharmacology*; Diterpenes/chemistry
  7. Abu N, Yeap SK, Pauzi AZ, Akhtar MN, Zamberi NR, Ismail J, et al.
    Front Pharmacol, 2016;7:89.
    PMID: 27065873 DOI: 10.3389/fphar.2016.00089
    The Fritillaria imperialis is an ornamental flower that can be found in various parts of the world including Iraq, Afghanistan, Pakistan, and the Himalayas. The use of this plant as traditional remedy is widely known. This study aims to unveil the anti-cancer potentials of Isopimara-7,15-Dien-19-Oic Acid, extracted from the bulbs of F. imperialis in cervical cancer cell line, HeLa cells. Flow cytometry analysis of cell death, gene expression analysis via cDNA microarray and protein array were performed. Based on the results, Isopimara-7,15-Dien-19-Oic acid simultaneously induced cell death and promoted cell survival. The execution of apoptosis was apparent based on the flow cytometry results and regulation of both pro and anti-apoptotic genes. Additionally, the regulation of anti-oxidant genes were up-regulated especially thioredoxin, glutathione and superoxide dismutase- related genes. Moreover, the treatment also induced the activation of pro-survival heat shock proteins. Collectively, Isopimara-7,15-Dien-19-Oic Acid managed to induce cellular stress in HeLa cells and activate several anti- and pro survival pathways.
    Matched MeSH terms: Diterpenes
  8. Leung AK, Barankin B, Leong KF, Hon KL
    Drugs Context, 2018;7:212563.
    PMID: 30622585 DOI: 10.7573/dic.212563
    Background: Penile warts are the most common sexually transmitted disease in males. Clinicians should be familiar with the proper evaluation and management of this common condition.

    Objective: To provide an update on the current understanding, evaluation, and management of penile warts.

    Methods: A PubMed search was completed in Clinical Queries using the key terms 'penile warts' and 'genital warts'. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews.

    Results: Penile warts are caused by human papillomavirus (HPV), notably HPV-6 and HPV-11. Penile warts typically present as asymptomatic papules or plaques. Lesions may be filiform, exophytic, papillomatous, verrucous, hyperkeratotic, cerebriform, fungating, or cauliflower-like. Approximately one-third of penile warts regress without treatment and the average duration prior to resolution is approximately 9 months. Active treatment is preferable to watchful observation to speed up clearance of the lesions and to assuage fears of transmission and autoinoculation. Patient-administered therapies include podofilox (0.5%) solution or gel, imiquimod 3.75 or 5% cream, and sinecatechins (polypheron E) 15% ointment. Clinician-administered therapies include podophyllin, cryotherapy, bichloroacetic or trichloroacetic acid, oral cimetidine, surgical excision, electrocautery, and carbon dioxide laser therapy. Patients who do not respond to first-line treatments may respond to other therapies or a combination of treatment modalities. Second-line therapies include topical/intralesional/intravenous cidofovir, topical 5-fluorouracil, and topical ingenol mebutate.

    Conclusion: No single treatment has been shown to be consistently superior to other treatment modalities. The choice of the treatment method should depend on the physician's comfort level with the various treatment options, the patient's preference and tolerability of treatment, and the number and severity of lesions. The comparative efficacy, ease of administration, adverse effects, cost, and availability of the treatment modality should also be taken into consideration.

    Matched MeSH terms: Diterpenes
  9. Ng AWR, Loh KK, Gupta N, Narayanan K
    Clin Nutr ESPEN, 2019 10;33:39-41.
    PMID: 31451273 DOI: 10.1016/j.clnesp.2019.07.014
    BACKGROUND & AIMS: Consumption of sugars in food and beverages has increased at an alarming rate. While excessive daily sugar intake has been well-associated as the onset of medical complications, additional sugars are still used in manufactured food products just to satisfy the consumers' needs. Hence, there is a need to develop sugar replacers that have low glycemic response without compromising the organoleptic characteristics of food products. This study aimed to determine if SUITENA™, a novel sweetener containing erythritol, xylitol, and Stevia, has low glycemic response upon consumption by human subjects.

    METHODS: Six human subjects were randomly chosen and were healthy at the point of experimentation. Capillary blood was collected via finger-prick method to monitor the glycemic response of every individual for 90 min after ingestion of sugar solution.

    RESULTS: It was found that the mean area under the curve (AUC) of the dextrose standard was 11.8-fold higher (p 

    Matched MeSH terms: Diterpenes, Kaurane
  10. Syukri Y, Taher M, Martien R, Lukitaningsih E, Nugroho AE, Zakaria ZA
    Adv Pharm Bull, 2021 Jan;11(1):171-180.
    PMID: 33747864 DOI: 10.34172/apb.2021.018
    Purpose:
    Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells.
    Methods:
    A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation.
    Results:
    ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND.
    Conclusion:
    ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.
    Matched MeSH terms: Diterpenes
  11. Jantan I, Ahmad W, Bukhari SN
    Front Plant Sci, 2015;6:655.
    PMID: 26379683 DOI: 10.3389/fpls.2015.00655
    The phagocyte-microbe interactions in the immune system is a defense mechanism but when excessively or inappropriately deployed can harm host tissues and participate in the development of different non-immune and immune chronic inflammatory diseases such as autoimmune problems, allergies, some rheumatoid disorders, cancers and others. Immunodrugs include organic synthetics, biological agents such as cytokines and antibodies acting on single targets or pathways have been used to treat immune-related diseases but with limited success. Most of immunostimulants and immunosuppressants in clinical use are the cytotoxic drugs which possess serious side effects. There is a growing interest to use herbal medicines as multi-component agents to modulate the complex immune system in the prevention of infections rather than treating the immune-related diseases. Many therapeutic effects of plant extracts have been suggested to be due to their wide array of immunomodulatory effects and influence on the immune system of the human body. Phytochemicals such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids and glycosides, present in several plants, have been reported to be responsible for the plants immunomodulating properties. Thus the search for natural products of plant origin as new leads for development of potent and safe immunosuppressant and immunostimulant agents is gaining much major research interest. The present review will give an overview of widely investigated plant-derived compounds (curcumin, resveratrol, epigallocatechol-3-gallate, quercetin, colchicine, capsaicin, andrographolide, and genistein) which have exhibited potent effects on cellular and humoral immune functions in pre-clinical investigations and will highlight their clinical potential.
    Matched MeSH terms: Diterpenes
  12. Sing D, Banerjee S, Jana SN, Mallik R, Dastidar SG, Majumdar K, et al.
    Front Pharmacol, 2021;12:629833.
    PMID: 34025404 DOI: 10.3389/fphar.2021.629833
    Andrographis paniculata (Burm. F) Nees, has been widely used for upper respiratory tract and several other diseases and general immunity for a historically long time in countries like India, China, Thailand, Japan, and Malaysia. The vegetative productivity and quality with respect to pharmaceutical properties of Andrographis paniculata varies considerably across production, ecologies, and genotypes. Thus, a field deployable instrument, which can quickly assess the quality of the plant material with minimal processing, would be of great use to the medicinal plant industry by reducing waste, and quality grading and assurance. In this paper, the potential of near infrared reflectance spectroscopy (NIR) was to estimate the major group active molecules, the andrographolides in Andrographis paniculata, from dried leaf samples and leaf methanol extracts and grade the plant samples from different sources. The calibration model was developed first on the NIR spectra obtained from the methanol extracts of the samples as a proof of concept and then the raw ground samples were estimated for gradation. To grade the samples into three classes: good, medium and poor, a model based on a machine learning algorithm - support vector machine (SVM) on NIR spectra was built. The tenfold classification results of the model had an accuracy of 83% using standard normal variate (SNV) preprocessing.
    Matched MeSH terms: Diterpenes
  13. Yao LJ, Jalil J, Attiq A, Hui CC, Zakaria NA
    J Ethnopharmacol, 2018 Oct 11.
    PMID: 30316887 DOI: 10.1016/j.jep.2018.10.001
    ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia is one of the largest and notable genera in Annonaceae family. Polyalthia species have been widely used in folklore medicine for the treatment of rheumatic fever, gastrointestinal ulcer and generalized body pain. Numerous in vitro and in vivo studies on Polyalthia Species have also corroborated the significant anti-inflammatory potential of its extracts and secondary metabolites.

    AIM OF THE STUDY: This review is an attempt to assess the anti-inflammatory activity of Polyalthia species by giving critical appraisal and establishing evidences of their traditional uses. Moreover this review will highlight the lead compounds for future drug development that can serve as a potential anti-inflammatory drug with comparative efficacy and minimum side effects.

    MATERIALS AND METHODS: An extensive literature review, focusing the anti-inflammatory potential of Polyalthia species was conducted using the following databases: PubMed, ScienceDirect, SpringerLink, Ovid, Scopus and ProQuest, as well as the locally available books, journals and relevant documents. The reference lists of retrieved papers were also searched for additional studies.

    RESULTS: The Polyalthia species have shown significant anti-inflammatory activity through various mechanism of action. The most significant anti-inflammatory mechanism includes the inhibition of nuclear factor kappa B (NF-κB), prostaglandins (PGs), pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS). The data suggests that hydroxycleroda-3,13-dien-15,16-olide and 16-oxocleroda-3,13-dien-15-oic acid, quercetin, rutin, spinasterol, α-spinasterol, goniothalamin and (-)-5-hydroxygoniothalamin are the most potent anti-inflammatory compounds from Polyalthia species with comparable IC50 with positive controls.

    CONCLUSIONS: Numerous pharmacological studies have supported the use of Polyalthia species against pain, rheumatic fever, haemorrhages and inflammation in traditional medicine. Flavonoids, diterpenoids, sterols and styrylpyrones from genus Polyalthia are the most significant class of compounds with potent anti-inflammatory activity. Secondary metabolites from these classes should be brought into further research to fill the gaps of knowledge in pharmacokinetics, pharmacodynamics, bioavailability, and toxicity in order to convert the pre-clinical results into clinical data for further investigation.

    Matched MeSH terms: Diterpenes
  14. Sim LY, Abd Rani NZ, Husain K
    Front Pharmacol, 2019;10:677.
    PMID: 31275149 DOI: 10.3389/fphar.2019.00677
    The prevalence of allergic diseases such as asthma, allergic rhinitis, food allergy and atopic dermatitis has increased dramatically in recent decades. Conventional therapies for allergy can induce undesirable effects and hence patients tend to seek alternative therapies like natural compounds. Considering the fact above, there is an urgency to discover potential medicinal plants as future candidates in the development of novel anti-allergic therapeutic agents. The Lamiaceae family, or mint family, is a diverse plant family which encompasses more than 7,000 species and with a cosmopolitan distribution. A number of species from this family has been widely employed as ethnomedicine against allergic inflammatory skin diseases and allergic asthma in traditional practices. Phytochemical analysis of the Lamiaceae family has reported the presence of flavonoids, flavones, flavanones, flavonoid glycosides, monoterpenes, diterpenes, triterpenoids, essential oil and fatty acids. Numerous investigations have highlighted the anti-allergic activities of Lamiaceae species with their active principles and crude extracts. Henceforth, this review has the ultimate aim of compiling the up-to-date (2018) findings of published scientific information about the anti-allergic activities of Lamiaceae species. In addition, the botanical features, medicinal uses, chemical constituents and toxicological studies of Lamiaceae species were also documented. The method employed for data collection in this review was mainly the exploration of the PubMed, Ovid and Scopus databases. Additional research studies were obtained from the reference lists of retrieved articles. This comprehensive summarization serves as a useful resource for a better understanding of Lamiaceae species. The anti-allergic mechanisms related to Lamiaceae species are also reviewed extensively which aids in future exploration of the anti-allergic potential of Lamiaceae species.
    Matched MeSH terms: Diterpenes
  15. Manikam SD, Manikam ST, Stanslas J
    J Pharm Pharmacol, 2009 Jan;61(1):69-78.
    PMID: 19126299 DOI: 10.1211/jpp/61.01.0010
    The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2).
    Matched MeSH terms: Diterpenes/isolation & purification; Diterpenes/pharmacology*; Diterpenes/chemistry
  16. Mohd-Radzman NH, Ismail WI, Jaapar SS, Adam Z, Adam A
    PMID: 24391675 DOI: 10.1155/2013/938081
    Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p < 0.001) in normal conditions and up to 4.4 times (p < 0.001) in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.
    Matched MeSH terms: Diterpenes, Kaurane
  17. Mei Y, Hu H, Deng L, Sun X, Tan W
    Sci Rep, 2022 Jul 27;12(1):12857.
    PMID: 35896572 DOI: 10.1038/s41598-022-16119-0
    Isosteviol sodium (STVNa) is a beyerane diterpene synthesized via acid hydrolysis of stevioside, which can improve glucose and lipid metabolism in animals with diabetes. However, it remains unknown whether STVNa can exhibit a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. We hypothesize that autophagic initiation may play a key role in mediating the development of NAFLD. Herein, we assessed the effects of STVNa on NAFLD and its underlying mechanisms. The results demonstrated that STVNa treatment effectively ameliorated NAFLD in rats fed high-fat diet (HFD). Moreover, STVNa decreased the expression of inflammation-related genes and maintained a balance of pro-inflammatory cytokines in NAFLD rats. STVNa also reduced lipid accumulation in free fatty acid (FFA)-exposed LO2 cells. In addition, STVNa attenuated hepatic oxidative stress and fibrosis in NAFLD rats. Furthermore, STVNa enhanced autophagy and activated Sirtuin 1/adenosine monophosphate-activated protein kinase (Sirt1/AMPK) pathway both in vivo and in vitro, thus attenuating intracellular lipid accumulation. In summary, STVNa could improve lipid metabolism in NAFLD by initiating autophagy via Sirt1/AMPK pathway. Therefore, STVNa may be an alternative therapeutic agent for treatment of NAFLD.
    Matched MeSH terms: Diterpenes, Kaurane
  18. Achoui M, Heyninck K, Looi CY, Mustafa AM, Haegeman G, Mustafa MR
    Drug Des Devel Ther, 2014;8:1993-2007.
    PMID: 25349474 DOI: 10.2147/DDDT.S68659
    The terpenoid 17-O-acetylacuminolide (AA) was shown to inhibit the production of several inflammatory mediators. However, the mechanisms by which this compound elicited its anti-inflammatory activity remain to be elucidated. In this study, we analyzed the effects of AA on inflammatory gene expression in two different cell types with primordial importance in the inflammatory processes - endothelial cells and macrophages. In human umbilical vein endothelial cells, AA inhibited the expression of inflammatory proteins including the adhesion molecules intercellular adhesion molecule 1; vascular cell adhesion molecule 1; and E-selectin, as well as the release of the chemokine interleukin-8. Additionally, AA hindered the formation of capillary-like tubes in an in vitro model of angiogenesis. AA's effects in endothelial cells can be attributed at least in part to AA's inhibition of tumor necrosis factor alpha-induced nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)'s translocation. Also, in lipopolysaccharide-stimulated macrophage-like RAW264.7 cells, AA was able to downregulate the expression of the genes cyclooxygenase 2, inducible nitric oxide synthase, interleukin-6, and chemokine (C-C motif) ligand 2. Moreover, AA inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), IκB kinase (IKK), and the mitogen-activated protein kinases JNK, ERK, and p38. In conclusion, the present results further support the anti-inflammatory potential of AA in different models of inflammation.
    Matched MeSH terms: Diterpenes/pharmacology*
  19. Subramanian R, Asmawi MZ, Sadikun A
    Acta Biochim. Pol., 2008;55(2):391-8.
    PMID: 18511986
    There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study was to provide in vitro evidence for potential inhibition of alpha-glucosidase and alpha-amylase enzymes, followed by a confirmatory in vivo study on rats to generate a stronger biochemical rationale for further studies on the ethanolic extract of Andrographis paniculata and andrographolide. The extract showed appreciable alpha-glucosidase inhibitory effect in a concentration-dependent manner (IC(50)=17.2+/-0.15 mg/ml) and a weak alpha-amylase inhibitory activity (IC(50)=50.9+/-0.17 mg/ml). Andrographolide demonstrated a similar (IC(50)=11.0+/-0.28 mg/ml) alpha-glucosidase and alpha-amylase inhibitory activity (IC(50)=11.3+/-0.29 mg/ml). The positive in vitro enzyme inhibition tests paved way for confirmatory in vivo studies. The in vivo studies demonstrated that A. paniculata extract significantly (P<0.05) reduced peak blood glucose and area under curve in diabetic rats when challenged with oral administration of starch and sucrose. Further, andrographolide also caused a significant (P<0.05) reduction in peak blood glucose and area under the curve in diabetic rats. Hence alpha-glucosidase inhibition may possibly be one of the mechanisms for the A. paniculata extract to exert antidiabetic activity and indicates that AP extract can be considered as a potential candidate for the management of type 2 diabetes mellitus.
    Matched MeSH terms: Diterpenes/pharmacology*
  20. Wong HC, Wong CC, Sagineedu SR, Loke SC, Lajis NH, Stanslas J
    Cell Biol Toxicol, 2014 Oct;30(5):269-88.
    PMID: 25070834 DOI: 10.1007/s10565-014-9282-5
    3,19-(3-Chloro-4-fluorobenzylidene)andrographolide (SRJ23), a new semisynthetic derivative of andrographolide (AGP), exhibited selectivity against prostate cancer cells in the US National Cancer Institute (NCI) in vitro anti-cancer screen. Herein, we report the in vitro growth inhibition and mechanisms of cell cycle arrest and apoptosis induced by SRJ23.
    Matched MeSH terms: Diterpenes/pharmacology*
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links