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Fulltext The role of natural antioxidants in cisplatin-induced hepatotoxicity

Abd Rashid N, Abd Halim SAS, Teoh SL, Budin SB, Hussan F, Adib Ridzuan NR, et al.

Biomed Pharmacother, 2021 Dec;144:112328.
PMID: 34653753 DOI: 10.1016/j.biopha.2021.112328

Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.

Matched MeSH terms: Inflammation Mediators/metabolism
Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells

Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL

J Ethnopharmacol, 2018 May 10;217:187-194.
PMID: 29462698 DOI: 10.1016/j.jep.2018.02.025

ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aβ)-induced microglia-mediated neurotoxicity.
MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aβ-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits.
RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aβ-induced secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aβ-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins.
CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.

Matched MeSH terms: Inflammation Mediators/metabolism
Fulltext BDMC33, A curcumin derivative suppresses inflammatory responses in macrophage-like cellular system: role of inhibition in NF-κB and MAPK signaling pathways

Lee KH, Chow YL, Sharmili V, Abas F, Alitheen NB, Shaari K, et al.

Int J Mol Sci, 2012;13(3):2985-3008.
PMID: 22489138 DOI: 10.3390/ijms13032985

Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases.

Matched MeSH terms: Inflammation Mediators/metabolism
Celastrol attenuates inflammatory responses in adipose tissues and improves skeletal muscle mitochondrial functions in high fat diet-induced obese rats via upregulation of AMPK/SIRT1 signaling pathways

Abu Bakar MH, Shariff KA, Tan JS, Lee LK

Eur J Pharmacol, 2020 Sep 15;883:173371.
PMID: 32712089 DOI: 10.1016/j.ejphar.2020.173371

Accumulating evidence indicates that adipose tissue inflammation and mitochondrial dysfunction in skeletal muscle are inextricably linked to obesity and insulin resistance. Celastrol, a bioactive compound derived from the root of Tripterygium wilfordii exhibits a number of attributive properties to attenuate metabolic dysfunction in various cellular and animal disease models. However, the underlying therapeutic mechanisms of celastrol in the obesogenic environment in vivo remain elusive. Therefore, the current study investigated the metabolic effects of celastrol on insulin sensitivity, inflammatory response in adipose tissue and mitochondrial functions in skeletal muscle of the high fat diet (HFD)-induced obese rats. Our study revealed that celastrol supplementation at 3 mg/kg/day for 8 weeks significantly reduced the final body weight and enhanced insulin sensitivity of the HFD-fed rats. Celastrol noticeably improved insulin-stimulated glucose uptake activity and increased expression of plasma membrane GLUT4 protein in skeletal muscle. Moreover, celastrol-treated HFD-fed rats showed attenuated inflammatory responses via decreased NF-κB activity and diminished mRNA expression responsible for classically activated macrophage (M1) polarization in adipose tissues. Significant improvement of muscle mitochondrial functions and enhanced antioxidant defense machinery via restoration of mitochondrial complexes I + III linked activity were effectively exhibited by celastrol treatment. Mechanistically, celastrol stimulated mitochondrial biogenesis attributed by upregulation of the adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) signaling pathways. Together, these results further demonstrate heretofore the conceivable therapeutic mechanisms of celastrol in vivo against HFD-induced obesity mediated through attenuation of inflammatory response in adipose tissue and enhanced mitochondrial functions in skeletal muscle.

Matched MeSH terms: Inflammation Mediators/metabolism
Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Dey YN, Sharma G, Wanjari MM, Kumar D, Lomash V, Jadhav AD

Pharm Biol, 2017 Dec;55(1):53-62.
PMID: 27600166

CONTEXT: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders.
OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats.
MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon.
RESULTS: APME or APAE pretreatment significantly (p

Matched MeSH terms: Inflammation Mediators/metabolism
Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells

Chong YJ, Musa NF, Ng CH, Shaari K, Israf DA, Tham CL

J Ethnopharmacol, 2016 Nov 04;192:248-255.
PMID: 27404229 DOI: 10.1016/j.jep.2016.07.032

PHARMOCOLOGICAL RELEVANCE: 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), is a phloroglucinol compound found naturally in Melicope ptelefolia. Melicope ptelefolia has been used traditionally for centuries as natural remedy for wound infections and inflammatory diseases.
AIM OF THE STUDY: Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs).
MATERIALS AND METHODS: HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro-inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS-stimulated HUVECs was evaluated.
RESULTS: It was found that pretreatment with tHGA inhibited monocyte adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E2 (PGE2). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs.
CONCLUSION: As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases.

Matched MeSH terms: Inflammation Mediators/metabolism
Hepatoprotective mechanism of Lygodium microphyllum (Cav.) R.Br. through ultrastructural signaling prevention against carbon tetrachloride (CCl4)-mediated oxidative stress

Gnanaraj C, Shah MD, Song TT, Iqbal M

Biomed Pharmacother, 2017 Aug;92:1010-1022.
PMID: 28609838 DOI: 10.1016/j.biopha.2017.06.014

Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65μg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.

Matched MeSH terms: Inflammation Mediators/metabolism