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1.
Phytother Res ; 38(6): 2931-2961, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38600726

RESUMEN

The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.


Asunto(s)
Antiinflamatorios , Artritis Reumatoide , Inmunosupresores , Fitoquímicos , Artritis Reumatoide/tratamiento farmacológico , Humanos , Antiinflamatorios/farmacología , Fitoquímicos/farmacología , Animales , Inmunosupresores/farmacología , Fitoterapia
2.
Crit Rev Food Sci Nutr ; : 1-26, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619217

RESUMEN

Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.

3.
Phytother Res ; 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38372084

RESUMEN

Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action-particularly mangiferin (2), α-mangostin (3), and γ-mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.

4.
Crit Rev Food Sci Nutr ; 63(22): 5546-5576, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34955042

RESUMEN

Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.


Asunto(s)
Alcaloides , Plantas Medicinales , Plantas Medicinales/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fitoquímicos/farmacología , Fitoquímicos/metabolismo , Factores Inmunológicos/farmacología , Adyuvantes Inmunológicos/metabolismo , Inmunidad
5.
Curr Pharm Biotechnol ; 24(11): 1465-1477, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36545731

RESUMEN

BACKGROUND: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation. OBJECTIVE: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses. METHODS: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days. RESULTS: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4+ and CD8+ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH). CONCLUSION: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.


Asunto(s)
Annona , Catequina , Ratas , Animales , Ovinos , Inmunidad Humoral , Ratas Wistar , Muramidasa , Extractos Vegetales/farmacología , Ceruloplasmina , Catequina/farmacología , Especies Reactivas de Oxígeno , Espectrometría de Masas en Tándem , Integrinas , Hojas de la Planta
6.
Phytother Res ; 37(3): 1036-1056, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36343627

RESUMEN

The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Humanos , Antivirales/farmacología , Fitoquímicos/farmacología
7.
Phytochem Rev ; 22(1): 211-273, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36345416

RESUMEN

Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae) is a plant indigenous to Africa and South-East Asia. It is widely used in ethnomedicine to alleviate various diseases including hypertension, diabetes, rheumatism, jaundice, inflammation, fever, fractures, scabies, and urinary disorders. A total of 167 phytoconstituents, belonging to 12 different chemical categories, including alkaloids, flavonoids, terpenoids, and phenolic compounds have thus far been isolated from various parts of T. crispa. Numerous in vitro and in vivo investigations have already established the antidiabetic, anticancer, antiparasitic, antimicrobial, immunomodulatory, hepatoprotective, analgesic, antipyretic, antihyperuricemic, and pesticidal activity of this plant, as well as its effects on the cardiac and the central nervous system. Most pharmacological investigations to date have been carried out on plant extracts and fractions. The exact identity of the phytoconstituents responsible for the observed biological effects and their mode of action at the molecular level are yet to be ascertained. Toxicological studies have demonstrated that T. crispa is relatively safe, although dose-dependent hepatotoxicity is a concern at high doses. This review presents a comprehensive update and analysis on studies related to the ethnomedicinal uses, phytochemistry, pharmacological activity and toxicological profile of T. crispa. It provides some critical insights into the current scientific knowledge on this plant and its future potential in pharmaceutical research.

8.
Artículo en Inglés | MEDLINE | ID: mdl-36193138

RESUMEN

Previous studies have shown that the extracts of Curcuma mangga Valeton & Zijp rhizomes and Picria fel-terrae Lour. leaves could modulate cellular- and humoral-mediated immunity in macrophages and animal models. In the present study, the immunomodulatory effects of combined ethanol extracts of C. mangga rhizomes and P. fel-terrae leaves were investigated on cellular- and humoral-mediated immunity in Wistar rats and mice. The phytochemical constituents of the ethanol extracts of C. mangga and P. fel-terrae, and combined extracts were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Mice were orally administered with combined extracts of C. mangga and P. fel-terrae (1 : 1) at doses of 25, 50, and 100 mg/kg·bw for 7 days, and the carbon clearance method was used to investigate their phagocytosis activity. Wistar rats were treated orally with the combined extracts 72 h prior to sensitization with Staphylococcus aureus and continued for 14 days. The effect of extracts on delayed-type hypersensitivity (DTH) response was determined by the paw edema method, while the effects on antibody (IgG and IgM) and interleukin-2 (IL-2) production were analyzed using enzyme-linked immunosorbent assay (ELISA). Picfeltarraenin VI and ferruginol were the major components in the extracts of P. fel-terrae and C. mangga, respectively. The combined extracts at 1 : 1 ratio demonstrated a dose-dependent stimulation of both cellular- and humoral-mediated immunity in both animal models. The combined extracts displayed the strongest stimulation on DTH response and phagocytosis activity at 100 mg/kg·bw, which were comparable with those of the positive control, levamisole. IgG and IgM production and IL-2 release were also stimulated after treatment with extracts. The combined extracts of C. mangga and P. fel-terrae possess strong stimulatory activities on cellular- and humoral-mediated immunity and may be developed as a potential nutraceutical for the modulation of immune responses.

9.
J Ethnopharmacol ; 294: 115391, 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35589022

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens (Lour.) Merr. (GP) is a herbaceous plant that grows in Malaysia and other parts of Southeast Asia. The herb is consumed as a remedy for various inflammatory-associated diseases, such as cancer, rheumatism, hypertension, diabetes mellitus and hyperlipidemia. Scientific studies demonstrate that GP extract possesses cardioprotective and anti-inflammatory effects. Cardiovascular disease is mainly caused by atherosclerosis, and inflammation plays a major role in all phases of atherosclerosis. The early inflammatory events in atherogenesis are the activation of endothelial cells and the recruitment of monocytes. AIM OF THE STUDY: This study aimed to evaluate the inhibitory effect of 80% ethanol extract of GP leaves (GPE) on the adherence of monocytes to the activated human endothelial cells and its underlying mechanism. MATERIAL AND METHODS: Qualitative and quantitative analyses of the extract were carried out by using a validated HPLC and UHPLC-MS/MS methods. The MTT test was used to select the range of concentration of extract for this study. The effect of GPE on TNF-α-induced monocyte-endothelial interaction was determined by the in vitro adhesion assay. Expression of cell surface proteins (ICAM-1, VCAM-1) and phosphorylation of nuclear factor kappa B (NF-κB) were determined by western blot, while expression of a chemokine (MCP-1) was identified by an enzyme-linked immunosorbent assay. RESULTS: HPLC and UHPLC-MS/MS analyses indicated that GPE contained chlorogenic acid, nicotiflorin and astragalin as the major compounds. GPE at 20, 40 and 60 µg/mL concentrations showed a significant reduction in monocyte adherence to endothelial cells and expression of ICAM-1 and MCP-1. However, only GPE at concentrations of 40 and 60 µg/mL was able to reduce VCAM-1 expression. Furthermore, GPE significantly inhibited IKKα/ß, IκBα, NF-κB phosphorylation and NF-κB translocation. CONCLUSION: In conclusion, GPE may inhibit monocyte adherence to the activated endothelial cells and expression of ICAM-1, VCAM-1 and MCP-1, which are important proteins for monocyte-endothelial interaction, by suppressing the NF-κB signaling pathway. The results of this study support the traditional use of GPE to counteract inflammation-associated diseases and suggest that GP can be a potential source for bioactive compounds for the development of anti-inflammatory agents to prevent atherosclerosis.


Asunto(s)
Asteraceae , Aterosclerosis , Aterosclerosis/prevención & control , Adhesión Celular , Células Endoteliales/metabolismo , Humanos , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Monocitos/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal , Espectrometría de Masas en Tándem , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo
10.
Plants (Basel) ; 10(10)2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34685899

RESUMEN

Natural products from plants were extracted and widely studied for their activities against many disease conditions. The selection of the extracting solvent is crucial to develop selective and effective methods for the extraction and isolation of target compounds in the plant matrices. Pharmacological properties of plant extracts and their bioactive principles are related to their excellent solubility, stability, and bioavailability when administered by different routes. This review aims to critically analyze natural deep eutectic solvents (NADES) as green solvents in their application to improve the extraction performance of plant metabolites in terms of their extractability besides the stability, bioactivity, solubility, and bioavailability. Herein, the opportunities for NADES to be used in pharmaceutical formulations development including plant metabolites-based nutraceuticals are discussed.

11.
Pharm Biol ; 59(1): 1203-1215, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34493166

RESUMEN

CONTEXT: Gynura procumbens (Lour.) Merr. (Asteraceae) has been reported to have various pharmacological activities including anti-inflammatory effects. OBJECTIVE: This study sought to determine whether Gynura procumbens (GP) could improve vascular reactivity by suppressing inflammation in postmenopausal rats fed with five-times heated palm oil (5HPO) diet. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were randomly divided into sham [non-ovariectomized; grouped as control, GP extracts (250 and 500 mg/kg), atorvastatin (ATV, 10 mg/kg)] and postmenopausal (PM) groups [ovariectomized rats fed with 5HPO; grouped as PM, GP extracts (250 and 500 mg/kg) and ATV (10 mg/kg)]. Each group (n = 6) was either supplemented with GP extract or ATV orally once daily for 6 months. RESULTS: In comparison with the untreated PM group, 250 and 500 mg/kg GP supplementation to PM groups reduced the systolic blood pressure (103 ± 2.7, 86 ± 2.4 vs. 156 ± 7.83 mmHg, p < 0.05), intima-media thickness (101.28 ± 3.4, 93.91 ± 2.93 vs. 143.78 ± 3.31 µM), vasoconstriction percentage induced by phenylephrine (102.5%, 88.3%, vs. 51.8%), sICAM-1 (0.49, 0.26 vs. 0.56 pg/mL) and sVCAM-1 (0.39, 0.25 vs. 0.45 pg/mL). GP extract supplementation increased vasorelaxation percentage induced by acetylcholine (78.4% vs. 47.3%) and sodium nitroprusside (84.2% vs. 53.7%), increased changes in plasma nitric oxide level (1.25%, 1.31% vs. 1.9%), and suppressed the elevation of TNF-α (0.39 vs. 1.02 pg/mL), IL-6 (0.43 vs. 0.77 pg/mL) and CRP (0.29 vs. 0.69 ng/mL) in the PM groups. CONCLUSIONS: GP extract might improve vascular dysfunction by suppressing the inflammatory response, consequently preventing blood pressure elevation.


Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Posmenopausia , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Asteraceae/química , Atorvastatina/farmacología , Presión Sanguínea/efectos de los fármacos , Grosor Intima-Media Carotídeo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etanol/química , Femenino , Inflamación/patología , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos
12.
Front Pharmacol ; 12: 643119, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33995049

RESUMEN

Curcuma species (family: Zingiberaceae) are widely utilized in traditional medicine to treat diverse immune-related disorders. There have been many scientific studies on their immunomodulating effects to support their ethnopharmacological uses. In this review, the efficacy of six Curcuma species, namely, C. longa L., C. zanthorrhiza Roxb., C. mangga Valeton & Zijp, C. aeruginosa Roxb. C. zedoaria (Christm.) Roscoe, and C. amada Roxb., and their bioactive metabolites to modulate the immune system, their mechanistic effects, and their potential to be developed into effective and safe immunomodulatory agents are highlighted. Literature search has been carried out extensively to gather significant findings on immunomodulating activities of these plants. The immunomodulatory effects of Curcuma species were critically analyzed, and future research strategies and appropriate perspectives on the plants as source of new immunomodulators were discussed. Most of the pharmacological investigations to evaluate their immunomodulatory effects were in vivo and in vitro experiments on the crude extracts of the plants. The extracts were not chemically characterized or standardized. Of all the Curcuma species investigated, the immunomodulatory effects of C. longa were the most studied. Most of the bioactive metabolites responsible for the immunomodulating activities were not determined, and mechanistic studies to understand the underlying mechanisms were scanty. There are limited clinical studies to confirm their efficacy in human. Of all the bioactive metabolites, only curcumin is undergoing extensive clinical trials based on its anti-inflammatory properties and main use as an adjuvant for the treatment of cancer. More in-depth studies to understand the underlying mechanisms using experimental in vivo animal models of immune-related disorders and elaborate bioavailability, preclinical pharmacokinetics, and toxicity studies are required before clinical trials can be pursued for development into immunomodulatory agents.

13.
Front Pharmacol ; 12: 660083, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33927634

RESUMEN

Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa and it is an immunoglobulin E-mediated disease. The incidence and prevalence of AR globally have been escalating over recent years. Antihistamines, intranasal corticosteroids, decongestants, intranasal anticholinergics, intranasal cromolyn, leukotriene receptor antagonists and immunotherapy have been used in the treatment of AR. However, there is a need to search for more effective and safer remedies as many of the current treatments have reported side effects. Medicinal plants have been used traditionally to relief symptoms of AR but their efficacy and safety have not been scientifically proven. In this review, up-to-date reports of studies on the anti-allergic rhinitis of several medicinal plants and their bioactive metabolites through suppression of the immune system are compiled and critically analyzed. The plant samples were reported to suppress the productions of immunoglobulin E, cytokines and eosinophils and inhibit histamine release. The suppression of cytokines production was found to be the main mechanistic effect of the plants to give symptomatic relief. The prospect of these medicinal plants as sources of lead molecules for development of therapeutic agents to treat AR is highlighted. Several bioactive metabolites of the plants including shikonin, okicamelliaside, warifteine, methylwarifteine, luteolin-7-O-rutinoside, tussilagone, petasin, and mangiferin have been identified as potential candidates for development into anti-allergic rhinitis agents. The data collection was mainly from English language articles published in journals, or studies from EBSCOHOST, Medline and Ovid, Scopus, Springer, and Google Scholar databases from the year 1985-2020. The terms or keywords used to find relevant studies were allergic rhinitis OR pollinosis OR hay fever, AND medicinal plant OR single plant OR single herb OR phytotherapy. This comprehensive review serves as a useful resource for medicinal plants with anti-allergic rhinitis potential, understanding the underlying mechanisms of action and for future exploration to find natural product candidates in the development of novel anti-allergic rhinitis agents.

14.
Curr Pharm Biotechnol ; 22(2): 262-273, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32532192

RESUMEN

BACKGROUND: The anticancer effects of Phyllanthus amarus extract on various cancer cells have been investigated, however, the effects of its major constituents on HCT116 human colorectal cancer cells have not been reported. OBJECTIVE: In the present study, we investigated the cytotoxic effect of 80% ethanol extract of P. amarus and its marker constituents (phyllanthin, hypophyllanthin, gallic acid, niranthin, greraniin, phyltetralin, isolintetralin, corilagin and ellagic acid) on HCT116 and their underlying mechanisms of action. METHODS: Their antiproliferative and apoptotic effects on HCT 116 were performed using MTT assay and flow cytometric analysis, respectively, while caspases 3/7, 8 and 9 activities were examined using the colorimetric method. The expression of cleaved poly ADP ribose polymerase enzyme (PARP) and cytochrome c proteins was investigated by the immune-blot technique. RESULTS AND DISCUSSION: HPLC and LC-MS/MS analyses demonstrated that the extract contained mainly lignans and polyphenols. The plant samples markedly suppressed the growth and expansion of HCT116 cells in a concentration- and time-dependent manner with no toxicity against normal human fibroblast CCD18 Co. P. amarus extract, phyllanthin and gallic acid induced mode of cell death primarily through apoptosis as confirmed by the exteriorization of phosphatidylserine. Caspases 3/7, 8, and 9 activities increased in a concentration-dependent manner following 24h treatment. The expressions of cleaved PARP (Asp 214) and cytochrome c were markedly upregulated. CONCLUSION: P. amarus extract, phyllanthin and gallic acid exhibited an apoptotic effect on HCT116 cells through the caspases-dependent pathway.


Asunto(s)
Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Neoplasias del Colon/enzimología , Lignanos/farmacología , Phyllanthus , Extractos Vegetales/farmacología , Polifenoles/farmacología , Apoptosis/fisiología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Cromatografía Liquida/métodos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Células HCT116 , Humanos , Lignanos/aislamiento & purificación , Lignanos/uso terapéutico , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Polifenoles/aislamiento & purificación , Polifenoles/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Espectrometría de Masas en Tándem/métodos
15.
Front Pharmacol ; 11: 504624, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33328981

RESUMEN

Background: Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as "Gynura," "antioxidant," "anti-inflammatory," or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

16.
BMC Complement Med Ther ; 20(1): 245, 2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32762741

RESUMEN

BACKGROUND: Immunomodulatory effects of Tinospora crispa have been investigated due to its traditional use to treat several inflammatory disorders associated to the immune system. The present study reports the underlying mechanisms involved in the stimulation of 80% ethanol extract of T. crispa stems on pro-inflammatory mediators release in lipopolysaccharide (LPS)-primed U937 human macrophages via MyD88-dependent pathways. METHODS: Release of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and production of prostaglandin E2 (PGE2) were determined by using enzyme-linked immunosorbent assay (ELISA). Immunoblot technique was executed to determine the activation of MAPKs molecules, NF-κB, PI3K-Akt and cyclooxygenase-2 (COX-2) protein. Determination of pro-inflammatory cytokines and COX-2 relative gene expression levels was by performing the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A reversed-phase HPLC method was developed and validated to standardize the T. crispa extract and chemical profiling of its secondary metabolites was performed by LC-MS/MS. RESULTS: Qualitative and quantitative analyses of chromatographic data indicated that syringin and magnoflorine were found as the major components of the extract. T. crispa-treatment prompted activation of NF-κB by enhancing IKKα/ß and NF-κB (p65) phosphorylation, and degradation of IκBα. The extract upregulated COX-2 protein expression, release of pro-inflammatory mediators and MAPKs (ERK, p38 and JNK) phosphorylation as well as Akt dose-dependently. T. crispa extract also upregulated the upstream signaling adaptor molecules, toll-like receptor 4 (TLR4) and MyD88. T. crispa-treatment also upregulated the pro-inflammatory markers mRNA expression. CONCLUSION: The results suggested that T. crispa extract stimulated the MyD88-dependent signaling pathways by upregulating the various immune inflammatory related parameters.


Asunto(s)
Mediadores de Inflamación/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tinospora , Regulación hacia Abajo , Humanos , Lipopolisacáridos , Malasia , Tallos de la Planta , Transducción de Señal , Células U937 , Regulación hacia Arriba
17.
BMC Complement Med Ther ; 20(1): 202, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32611404

RESUMEN

BACKGROUND: Phyllanthus amarus has been shown to attenuate lipopolysaccharide (LPS)-induced peripheral inflammation but similar studies in the central nervous system are scarce. The aim of the present study was to investigate the neuroprotective effects of 80% ethanol extract of P. amarus (EPA) in LPS-activated BV2 microglial cells. METHODS: BV2 microglial cells c for 24 h, pre-treated with EPA for 24 h prior to LPS induction for another 24 h. Surface expression of CD11b and CD40 on BV2 cells was analyzed by flow cytometry. ELISA was employed to measure the production of pro-inflammatory mediators i.e. nitric oxide (NO) and tumor necrosis factor (TNF)-α. Western blotting technique was used to determine the expression of inducible nitric oxide synthase (iNOS), myeloid differentiation protein 88 (MYD88), nuclear factor kappa B (NF-κB), caspase-1, and mitogen activated protein kinase (MAPK). RESULTS: Qualitative and quantitative analyses of the EPA using a validated ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method indicated the presence of phyllanthin, hypophyllanthin, niranthin, ellagic acid, corilagin, gallic acid, phyltetralin, isolintetralin and geraniin. EPA suppressed the production of NO and TNFα in LPS-activated BV2 microglial cells. Moreover, EPA attenuated the expression of MyD88, NF-κB and MAPK (p-P38, p-JNK and p-ERK1/2). It also inhibited the expression of CD11b and CD40. EPA protected against LPS-induced microglial activation via MyD88 and NF-κB signaling in BV2 microglial cells. CONCLUSIONS: EPA demonstrated neuroprotective effects against LPS-induced microglial cells activation through the inhibition of TNFα secretion, iNOS protein expression and subsequent NO production, inhibition of NF-κB and MAPKs mediated by adapter protein MyD88 and inhibition of microglial activation markers CD11b and CD40.


Asunto(s)
Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Fármacos Neuroprotectores/farmacología , Phyllanthus , Extractos Vegetales/farmacología , Animales , Línea Celular , Inflamación/tratamiento farmacológico , Lipopolisacáridos , Malasia , Ratones , Microglía/efectos de los fármacos , Óxido Nítrico/metabolismo
18.
Inflammopharmacology ; 28(1): 1-18, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31792765

RESUMEN

The causal and functional connection between inflammation and cancer has become a subject of much research interest. Modulation of cell signaling pathways, such as those involving mitogen activated protein kinases (MAPKs), nuclear factor kappa ß (NF-κB), phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt), and Wnt, and their outcomes play a fundamental role in inflammation and cancer. Activation of these cell signaling pathways can lead to various aspects of cancer-related inflammation. Hence, compounds able to modulate inflammation-related molecular targets are sought after in anticancer drug development programs. In recent years, plant extracts and their metabolites have been documented with potential in the prevention and treatment of cancer and inflammatory ailments. Plants possessing anticancer and anti-inflammatory properties due to their bioactive constituents have been reported to modulate the molecular and cellular pathways which are related to inflammation and cancer. In this review we focus on the flavonoids (astragalin, kaempferol, quercetin, rutin), lignans (phyllanthin, hypophyllanthin, and niranthin), tannins (corilagin, geraniin, ellagic acid, gallic acid), and triterpenes (lupeol, oleanolic acid, ursolic acid) of Phyllanthus amarus, which exert various anticancer and anti-inflammatory activities via perturbation of the NF-κB, MAPKs, PI3K/Akt, and Wnt signaling networks. Understanding the underlying mechanisms involved may help future research to develop drug candidates for prevention and new treatment for cancer and inflammatory diseases.


Asunto(s)
Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Phyllanthus/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Humanos
19.
Bioinformation ; 15(8): 535-541, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31719762

RESUMEN

Phyllanthus amarus Schumach. and Thonn. is a wide spread medicinal herb with various traditional uses. It is well documented for its antioxidant, anti-inflammatory, and hepatoprotective activities. Therefore, it is of interest to evaluate the 80% ethanol extract of Phyllanthus amarus (PA) on spatial memory using the 8-radial arm maze (8-RAM) in mice after induction of neuro inflammation by lipopolysaccharide (LPS) in a 14- and 28-days treatment study. LC-MS/MS was performed to profile the chemical composition in PA extract. Mice were treated orally with 5% v/v tween 20, PA extract (100, 200 and 400 mg/kg), or ibuprofen (IBF 40 mg/kg) for 14 and 28 days. All groups were challenged with LPS (1 mg/kg) via intraperitoneal (i.p.) injection a day prior to the 8-RAM task except for the negative control group which received an i.p. injection of saline. Data obtained were analyzed with one-way ANOVA followed by post hoc Dunnett's test (comparison of all groups against vehicle control). Analysis of LC-MS/MS data revealed the presence of 16 compounds in the PA extract. Administration of PA extract at 200 and 400 mg/kg for 14 and 28 days significantly (*P<0.05) decreased the working and reference memory errors against LPS-induced spatial memory impairment. The observed protective action is possibly due to the putative antineuroinflammatory effects of PA. In conclusion, PA extract possess neuroprotective effects against spatial memory impairment mediated by LPS.

20.
BMC Complement Altern Med ; 19(1): 331, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31752812

RESUMEN

BACKGROUND: Zingiber zerumbet rhizome and its bioactive metabolites have previously been reported to exhibit innumerable pharmacological properties particularly anti-inflammatory activities. In the present study, the 80% ethanol extract, essential oil and zerumbone of Z. zerumbet rhizomes were explored for their in vitro immunosuppressive properties on chemotaxis, CD11b/CD18 expression, phagocytosis and chemiluminescence of isolated human polymorphonuclear neutrophils (PMNs). METHODS: The extract was analyzed quantitatively by performing a validated reversed phase high performance liquid chromatography (RP-HPLC). Zerumbone was isolated by chromatographic technique while the essential oil was acquired through hydro-distillation of the rhizomes and further analyzed by gas chromatography (GC) and GC-MS. Chemotaxis assay was assessed by using a 24-well cell migration assay kit, while CD18 integrin expression and phagocytic engulfment were measured using flow cytometry. The reactive oxygen species (ROS) production was evaluated by applying lucigenin- and luminol-enhanced chemiluminescence assays. RESULTS: Zerumbone was found to be the most abundant compound in the extract (242.73 mg/g) and the oil (58.44%). Among the samples tested, the oil revealed the highest inhibition on cell migration with an IC50 value of 3.24 µg/mL. The extract, oil and zerumbone showed moderate inhibition of CD18 integrin expression in a dose-dependent trend. Z. zerumbet extract showed the highest inhibitory effect on phagocytic engulfment with percentage of phagocytizing cells of 55.43% for PMN. Zerumbone exhibited strong inhibitory activity on oxidative burst of zymosan- and PMA-stimulated neutrophils. Zerumbone remarkably inhibited extracellular ROS production in PMNs with an IC50 value of 17.36 µM which was comparable to that of aspirin. CONCLUSION: The strong inhibition on the phagocytosis of neutrophils by Z. zerumbet extract and its essential oil might be due the presence of its chemical components particularly zerumbone which was capable of impeding phagocytosis at different stages.


Asunto(s)
Inmunosupresores/farmacología , Neutrófilos/efectos de los fármacos , Aceites Volátiles/farmacología , Fagocitosis/efectos de los fármacos , Sesquiterpenos/farmacología , Zingiberaceae/química , Supervivencia Celular , Células Cultivadas , Quimiotaxis/efectos de los fármacos , Humanos , Extractos Vegetales/farmacología
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