THE ANTI-INFLAMMATORY ACTIVITY OF PLANT DERIVED INGREDIENTS: AN ANALYTICAL REVIEWHTML Full Text
THE ANTI-INFLAMMATORY ACTIVITY OF PLANT DERIVED INGREDIENTS: AN ANALYTICAL REVIEW
Department of Zoology, A.P.C. Roy Government College, Himanchal Vihar, Matigara, Siliguri, Darjeeling - 734010, West Bengal, India.
ABSTRACT: Inflammation, a protective response, can be dangerous if left untreated. The current synthetic anti-inflammatory drugs available in the market are coupled with various side effects. Plant-derived products can serve as a better alternative being cheap, easily available and having very few side effects. A sizable number of plants having anti-inflammatory activity have been studied. The crude extract of the plant is easy to obtain but it is not possible to indicate the component responsible for a particular property of the extract as it is a mixture of various components. Therein lays the importance of isolating the active principles from the crude extract and studying their mechanism of action. The present study aspires to provide an insight into the current trend of treatment of inflammation using herbal remedies by highlighting the different active principles obtained from different parts of plants, their concentrations used in specific test systems alongside underlining their molecular mode of action.
Anti-inflammatory, Plant products, Active components, Mechanism of action
INTRODUCTION: Inflammation is defined as the response shown by the body when it is invaded by an antigen or any type of damage (physical, chemical or traumatic) occurs 1. It is a naturally resolving process in which body fluid, proteins, and cells from the blood are transferred to the damaged tissues for their removal and resolution of the area. The inflammatory response is initiated by temporary vasoconstriction which is followed by acute vascular response due to increased blood flow leading to edema 2. The acute cellular response occurs over the next few hours and is characterized by infiltration of neutrophils into the damaged area.
If the damage is severe, chronic cellular response follows and is characterized by appearance of macrophages and lymphocytes. Over a few weeks, normal tissue design is restored. When the immune system is unable to restore the body to the original state because of the presence of a large amount of antigen or inaccessibility of the antigen, persistent inflammation occurs, and treatment becomes essential.
Immune Components Responsible for Inflammation: Both cells and soluble components act as mediators of inflammation. The vasoactive amines, reactive oxygen species, arachidonic acid derivatives, etc. are some of the mediators responsible for the propagation of inflammation. The cells include macrophages, eosinophils, neutrophils, etc. Some of the mediators are described below:
Arachidonic Acid Derivatives: Prostaglandin E2 (PGE2) is responsible for the pain and edema which occurs during inflammation 3. It is formed when cycloxygenase (mainly COX-2, which is inducible and plays an important role; COX-1 being constitutive) acts on arachidonic acid 4. Cycloxygenase, in turn, is activated by nitric oxide (NO), another molecule of great importance, synthesized by inducible nitric oxide synthase (iNOS) 5. The lipoxygenase pathway is also activated during inflammation to produce leukotrienes. Both the pathways activate various kinins, neuro-peptides, and histamine, as well as complement components, along with cytokines and free radicals.
Cytokines: Cytokines are proteins, secreted by white blood cells which play a critical role in inflammation by regulating inflammatory mediators usually secreted by other cells 6. Pro-inflammatory cytokines aggravate inflammation while anti-inflammatory cytokines down-regulate the same. Pro-inflammatory cytokines include IL-1β, IL-6, IL-12 and TNF-a while anti-inflammatory cytokines include IL-10, IL-4, etc. 7
Oxidative Status and Anti-oxidant Enzymes: Generation of reactive oxygen species (ROS) like superoxide, peroxynitrite, nitric oxide, etc. are greatly increased in inflammation causing damage to the cell components 8. To minimize damage, cells have evolved enzymatic (catalase, superoxide dismutase) and non-enzymatic (glutathione) defense mechanisms but are downregulated during inflammation 9.
Signaling Pathways: NF-κB is a transcription factor which plays an important role in inflammation as it controls the expression of NO, COX-2 and pro-inflammatory cytokines 10. It remains in the cytoplasm rendered inactive by IκB. When activated, IκB is phosphorylated and degraded, and NF-κB binds to DNA after entering the nucleus, allowing transcription of iNOS mRNA and various other pro-inflammatory cytokines. The activation of NF-κB occurs via the activation of mitogen-activated protein kinases (MAPKs) which include p38 MAPK (p38), extracellular signal-regulated kinases 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) 11, 12.
Current Anti-inflammatory Drugs are Associated with Side Effects: The control of inflammation includes synthetic anti-inflammatory drugs that can be given orally. They include the non-steroidal anti-inflammatory drugs (NSAIDs), steroids and disease-modifying antirheumatic drugs (DMARDs) 13. The NSAIDs results in relief of pain by inhibiting cycloxygenases but are associated with side effects like headache, giddiness, abdominal pain, gastric ulcer, abnormal liver function, etc. 13
Other than the general symptoms some drugs are associated with specific symptoms like Flurbiprofen is associated with cogwheel rigidity and Ibuprofen with agranulocytosis and aplastic anemia 14. The major steroids used for the treatment of inflammation are glucocorticoids which reduces bone erosions but cause suppression of T cells, extreme changes in mood, headache, giddiness, extreme changes in mood, seizures, etc. 15 The DMARDs slows down the disease by suppression of the immune system which in itself is a disadvantage. TNF-α blocking agents are associated with increased bacterial infections.
Alternate Anti-Inflammatory Drugs from Natural Flora: As the market available drugs pose danger to the human body 16, the search for a natural product is essential as it would be less toxic but equally effective. Research is currently concentrated in this area and herein lays the importance of India being a treasure trove of medicinal plants by virtue of its being a mega diversity country. Plant products are therefore easily available and are a cheap option in India. The properties of the medicinal plants were well documented in Ancient Indian Literature and practiced in Ayurveda and other traditional forms of treatment.
MATERIALS AND METHODS: The names of the plants having anti-inflammatory properties were identified from a myriad of books on medicinal plants and also searched in an online database by entering the name of the plant along with the word “anti-inflammatory”. The plants having anti-inflammatory properties were then separately searched in Pubmed, Google, Science Direct etc to see whether their active components were isolated and the mechanism of action studied. The information accumulated on the active ingredients and their mode of action were then represented in a table format.
RESULTS AND DISCUSSION:
Active Ingredients Obtained from Plants and Their Mechanism of Action: The plants manifesting anti-inflammatory properties are listed Table 1 along with their mechanism of action. Most of the anti-inflammatory properties of plants are ascribed to phenols derived from the secondary metabolism of plants. Phenolic compounds are grouped into flavonoids, composed of two aromatic rings linked through an oxygen heterocycle, and non-flavonoids, commonly known as phenolic acids 17. Flavonoids possess significant anti-inflammatory activity 18.
Active Ingredients: Some components namely cirsimarin (Cirsium japonicum) 19, eucalyptol (Eucalyptus sp.) 20, allylpyrocatechol (Piper betle) 21, curcumin (Curcuma longa) 22, theanine (Camellia sinensis)23 etc. are obtained from specific one or two plants in which they are present as a major component or alongside other phenols. Most of them have various therapeutic properties. Since inflammation is associated with various diseases like rheumatoid arthritis, neurodegenerative diseases, heart diseases, gastric ulcers, cancer, etc., some of these components were able to relieve the symptoms of various diseases simply by inhibiting the mediators of inflammation or by upregulating the anti-oxidant properties of the organism besides acting on specific targets of the respective diseases Table 1.
Animals/Cell Lines Used: Various strains of rat (Sprague Dawley, Wistar, etc.) and mice (ICR, C57BL/6, BALB/c, etc.) were the common choices as models of inflammation wherein inflammation was induced by lipopolysaccharide, pro-inflam-matory cytokines or other phlogistic agents. Lipopolysaccharide was used in maximum number of cases. The drug of choice is given orally in most cases and then the plasma/tissues/cells are collected for analyzing the effect of the drug. Histological studies of the affected tissues using common stains were done in many cases to prove the efficacy of the herbal drugs. For in-vitro studies, mouse peritoneal cells or cell lines were used. RAW264.7 is the general choice for study of the anti-inflammatory activity of the plant product (though other cell lines like THP-1 and U937 were also used) while more specific cell types (BV2 microglial cells, human umbilical vein endothelial cells, human lung cancer cell, etc.) were chosen for studying the anti-inflammatory effect related to a particular disease Table 1.
TABLE 1: PLANTS HAVING ANTI-INFLAMMATORY PROPERTIES AND THEIR MECHANISM OF ACTION
|Plant-derived product||Part of plant||Test
|Concentration||Molecular mechanism(s) of
|Caffeic acid, S-allyl cysteine, and uracil from Allium sativum||Bulb||HR-1 hairless mice||5-20 μM||Inhibited DCFDA induced ROS production. Inhibited degradation of type1 procollagen and expression of MMP 3 and 9. Uracil inhibited COX-2 and Inos. Others inhibited NF-κB and AP-1 activity24|
|S-allyl cysteine||Wistar rats
|25-100 mg/kg b.w.
0.01- 0.1 mM
|Improved spatial recognition memory. Inhibited MDA and increased SOD, catalase and GSH levels. Inhibited glial fibrillary acidic protein, IL-6, IL-1β, Nox, NF-κB, IL-1 β and TLR4 activity. Upregulated Nrf2 activity25, 26|
|Alliin||3T3-L1 adipocytes||100 μmol/L||Inhibited LPS induced IL-6, MCP-1, Egr-1. Inhibited phosphorylation of ERK1/2 upregulation of genes involved in immune response27|
|Thiacremonone||ICR/(APP/ PS1) transgenic mice: attenuated cognitive impairments. BV-2 microglia cells. Cortical neuronal cells from Sprague Dawley rats||1-10 mg/kg b.w.,
|Inhibited ROS and NO, iNOS, COX-2 and GFAP expression. Inhibited amyloid β, NF-κB and ERK activity. Inhibited BACE level brains and augmented peroxiredoxin 6 (PRDX6)28, 29|
|Hirsutenone from Alnus sp.||Bark||Human keratinocytes HEK001
|1 – 10 μM
IC50: 14.08 μM
|Reduced NO, IL-1 β, IL-8, CCL17 and scavenged free radicals. Reduced activation of TLR-4, NF-κB and ERK phosphorylation30, 31|
|Antcin A from Antrodia camphorata||Fruiting bodies||Human lung cancer cell A549||10 mol/L||Induced nuclear migration of glucocorticoid receptor. Successfully docked to the binding cavity of GR32|
|Antrocamphin A||RAW264.7 cells||1-20 μg/ml,
20 mg/ ml
|Inhibited NO, iNOS, COX-2 and superoxide. Inhibited platelet aggregation. Inhibited NF- κB activation 33, 34|
|Arctigenin from Arctium lappa||Seed||C57BL/6 mice peritoneal macrophages C57BL/6 mice||5 mg/kg b.w.
25-50 mg/kg b.w.
|Inhibited IL-1β, IL-6, TNF-α, MIP-2, MCP-1, MAdCAM-1, ICAM-1, and VCAM-1 increased IL-10 and CD204 expression. Decreased MDA level but increased SOD and GSH levels. Inhibited PI3K, AKT, IKKβ, NF-κB and MAP kinase activity35, 36|
|3-acetyl-11-keto-β-boswellic acid from Boswellia serrata||Gum resin||KBM-5, RAW 264.7, H1299, HEK A293, HCC4 and MDA 1986 cells, Albino rats||10-50 μM
|Inhibited COX-2, IL-6, and TNF-α. Reduced TNF-α induced NF- κB. Blocked NF- κB activation and increased dopamine levels 37, 38|
|Cajaninstilbene acid from Cajanus cajan||Leaves||RAW264.7 cells
U937, Zebrafish Larvae
|25 -100 μg/ml
|Activated PPARγ. Inhibited NO, iNOS, IL-6, and TNF-α. Inhibited migration of neutrophils and macrophages. Inhibit NF-κB and MAP kinase activation 39, 40|
|Epigallocatechin-3-gallate (green tea) from Camellia sinensis||Leaves||Fibroblast cells
BALB/c mice: reduced OVA-induced nasal rubbing and sneezing
|Inhibited COX-2, TNF-α, IL-4, IL-1β,
and IL-6 41, 42
|Theaflavin (black tea)||C57BL/6 mice
U937 and RAW264.7 cells
Gingival keratinocytes: enhanced tight junction integrity
|20-40 mg/kg bw
6.25-50 mM/7.9-125 mg/ml
|Inhibited NF-κB, JNK, and p38 activity. Inhibited TNF-α, IL-1β, IL-6, chemokine (C-X-C) ligand 8, MMP-3, MMP-8 and MMP-9 43, 44|
|Thearubigin (black tea)||Mice: inhibited 2,4,6-trinitrobenzene sulfonic acid (TBNS) induced colitis||40-100 mg/kg b.w.||Inhibited TBNS induced NO, iNOS. Inhibited NF-κB activation 45|
|Theanine||ICR mice CD-1 mice: reduced TPA-induced erythema, vascular permeability increase, epidermal and dermal hyperplasia,||20- 40 mg/kg
|Decreased alanine aminotransferase, aspartate aminotransferase, SOD and MDA levels. Reduced neutrophil infiltration and PECAM-1. Decreased IL-1β, TNF-α, COX-2, iNOS, MMP-3 IFN-γ and increased IL-10. Decreased NF-κB activity 23, 46|
|Capsaicin from Capsicum sp.||Fruit||Human THP-1 cells||10 μM||Decreased LPS induced IL-1β, TNF-α and Il-6. Increased LXRα expression through PPARγ pathway and inhibiting NF-κB activity47|
|Cirsimarin from Cirsium japonicum||Aerial part||RAW 264.7 cells
|10-40 μM||Inhibited LPS induced NO, iNOS, COX-2, PGE2, TNF- α and IL-6. Downregulated phosphorylation of JAK and MAPK and nuclear translocation of interferon regulatory factor 3.19|
|Colchicine from Colchicum autumnale||Bulb like corms||Recurrent aphthous stomatitis (RAS) patients||0.5 mg||Decrease in level of neutrophil-lymphocyte ratio, white cell count and red cell distribution width. No change in mean platelet volume, Hb levels 48|
|Corynoline from Corydalis bungeana||Whole herb||RAW264.7 cells
Human umbilical vein endothelial cells
|Inhibited LPS-induced NO, iNOS, COX-2, IL-6, IL-10, TNF-α, IL-1β, VCAM-1 and ICAM-1. Increased expression of Nrf2, quinone oxidoreductase 1 and HO-1. Inhibited NF-κB, p38 and ERK49-51|
|Cudratricuxanthone A from Cudrania tricuspidata||Root||RINm5F
|1- 10 µM
0.058-0.294 mg/kg b. w.
|Inhibited ROS, NO, iNOS, IL-6, TNF-α and NF-κB. Reduced phosphorylation of STAT-1, 3 and 5. Inhibited glucose-stimulated insulin secretion. Reduced cecal ligation and puncture (CLP)-induced creatinine, blood urea nitrogen (BUN), lipid peroxidation52|
|Curcumin from Curcuma longa||Rhizome||BV2 microglial cells
RAW264.7, THP-1 cells
5 - 15 μM
0.15 -0.6 mg/ml
|Inhibited NO, iNOS, TNF-α, IL-6 and IL-1β. Improved ovalbumin-induced total WBC, PLA2, TP, IgE, IL-4, IFN-γ, IFN-γ/IL-4 ratio, SOD, thiol. Inhibited NF-κB, ERK, p38 pathway and p13K/AKT pathway22, 53, 54|
|Eucaluptol (1,8 cineole) from Eucalyptus sp||Leaves||Murine alveolar macrophage cell line MH-S (CRL 2019)
C57BL/6 and TRPM8 mice HEK293T cells
30-300 mg/kg b.w.
|Reduced IL-1α, IL-1β, TNF-α, IFN-γ and IL-6. Downregulated TREM -1 and NLRP3 pattern recognition receptors and enhanced phagocytic activity. Inhibited JNK1/2 and ERK1/2 activity 20, 55|
|Ginkgetin from Gikngo biloba||Leaves||Mouse bone marrow-derived mast cells, ICR mice: TPA induced ear edema||1.6- 50 µM
20—80 µg /ear/treatment
|Reduced PGD2, PGE2, COX-2 and IL-1β. Inhibited leukotriene and β-hexoseaminidase56, 57
|Alantolactone and isoalantolactone from Inula helenium,||roots||HaCat cells||0.6-2.4 μg/ml||Inhibited TNF-α-induced activation of NF-κB and the expression of TNF-α, IL-1, and IL-4.58|
|Scopariusols from Isodon scoparius||Aerial parts||RAW264.7 cells||IC50 value of 0.6 μmol·L-1||Inhibited LPS induced NO production59|
|Kalopanaxsaponin A from Kalopanax pictus||Stem bark||ICR mice: inhibited weight reduction, colon shortening, inflammation and thickening
Murine BV2 microglial cell
|10-20 mg/kg b.w.
|Inhibited LPS-induced iNOS, COX-2 IL-1β, TNF-α and IL-6, ROS and upregulated IL-10. Inhibited activation of IRAK-1, NF-κB, JNK, ERK and p38 and upregulated HO-1 60, 61|
|Momordin from Kochia scoparia||Fruits||RAW 264.7 cells||7.5-30 μg/ml
|Reduced NO, iNOS, COX-2, PGE2, IL-6 and TNF-α and NF-κ 62, 63|
|Thymoquinone from Nigella sativa||Seed||BV2 microglial cells
Wistar rats: Reduced neutrophil accumulation in pleural space
Human neutrophils C57BL/6: Reduced EtOH–induced gastritis, RAW264.7, and human monocyte-like U937
10-50 mg/kg b.w.
0- 25 µM
|Inhibited NO, iNOS, COX-2, TNF-α, IL-6, IL-1β IL-12p40/70, superoxide ion, CCL12 /MCP-5, CCL2/ MCP-1, and G-CSF, Cxcl10. Inhibited IRAK-1, AP-1, PKC, MAPK, and NF-κB. Impaired the phosphorylation on Ser-304 and Ser-328 of p47(PHOX), a cytosolic subunit of the NADPH oxidase64-66|
|Ginsenoside from Panax ginseng||Roots||Human airway epithelial cells
A549 cells, Intestinal epithelial cells (H-29); RAW264.7 cells
Sprague Dawley rats
|Reduced IL-1β, TNF-α, IL-6, NO, COX-2, ROS, MDA and caspase 3. Increased GSH, p-AKT/AKT, GSK 3β, and reduced p21WAF1/CIP1 and p53 proteins. Inhibition of NF- κB activity 67-69|
|Picroliv isolated from Picrorhiza kurroa
|Roots and rhizomes
|KBM 5 /H1299/A293 cells
|50- 150 μg/ml.
12.5 mg/kg b.w.
|Downregulated IL-1β, TNF-α, and NF-κB pathway. Suppressed IAP1, Bcl-2, Bcl-xL, survivin, and TRAF2, cyclin D1 and COX-2, VEGF, ICAM-1, and MMP-9. Inhibited MPO, MDA expression and increased SOD levels 70,71|
|Allylpyrocatechol from Piper betle||Leaves||Sprague Dawley rats: reduced paw edema.
RAW 264.7 cells
|10 mg/kg bw/ 20 mg/kg b.w.
2.5 and 5 mg/ml
|Inhibited NO and iNOS. Inhibited IL-12p40, TNF-a, IL-6 COX-2 and PGE2. Inhibited NF-κB
activation 21, 72
|Platycodin D from Platycodon granduflorum
|Sprague Dawley rats
bovine mammary epithelial cells (bMEC)
|10-30 mg/kg b.w.
|Attenuated cigarette smoke-induced/LPS induced MDA, NO, IL-6, TNF-α, and IL-1β. Decreased serum alanine transaminase, aspartate transaminase and total bilirubin. Attenuated cigarette smoke-induced pathological changes in lung. Down-regulated MD-2 and CD14. Attenuated TLR4, MyD88 and TRAF-6, NF-κB and upregulated LXRα expression 73-75|
|Cirsitakaoside from Premna szemaoensis||Stem and leaves||C57BL/6J mice
Mouse peritoneal macrophages and RAW264.7 cells
|Suppressed LPS induced activation of IL-1B, TNF-α, IL-6. Inhibited iNOS and COX-2 mRNA. Inhibited NF-KB and MAPK pathway 76|
|Punicalagin from Punica granatum||Fruit||ICR mice: prevented LPS induced memory impairment
Astrocytes and microglial BV-2 cells. Bovine endometrial epithelial cells (bEEc)
|1.5 mg/kg b.w.
|Inhibits LPS induced iNOS, COX-2, production of ROS, NO, TNF-α, IL-6, IL-8, and IL-1β. Suppress NF-κB, p38, JNK and ERK activity. Downregulated APP and BACE1 expression 77, 78|
|Tanshinone IIA from Salvia miltiorrhiza||Root||Human vascular endothelial cells (HUVEC)
30-60 mg/kg b.w.
|Attenuated IL-1β, TNF-α, COX-2, fractalkine/CX3CL1, VCAM-1, ICAM-1, GMCSF and AP-1. Reduced total cholesterol, triglyceride, LDL, VLDL, MDA. Inhibited adhesion of THP-1 monocytes. Inhibited ERK1/2 and NF-κB activity 79-81|
CD-1 mice: alleviate memory decline in Aβ1-42-injected mice
|10-7 to 10-5 M
1-10 mg/kg b.w.
|Reduced expression of NO iNOS COX-2 via ERβ-dependent and NF-kB pathway 82, 83|
|Salvianolic acid B||Wistar rats: improved cerebral ischemic injury PC-12 cells.
Sprague Dawley rats: Primary cortical neurons were obtained and LPS induced depression was reduced. C57BL/6: suppressed cartilage destruction and slowed osteoarthritis development
Human OA chondrocytes
20 mg/kg b.w.
25 mg/kg b.w.
|Reduced chemical and oxygen-glucose deprivation and reoxygenation (OCD/R) IL-1β, IL-6, TNF-α, NO, PGE2, INOS, COX-2, MMP-13 and ADAMTS-5. Inhibited TLR4/MyD88/TRAF6 signaling ameliorated NeuN release. Induced autophagy and decreased NLRP3 inflammasome activation. Inhibited NF-κB activity 84-86|
|Saurolactum from Saururus chinensis
|Roots||RAW 264.7 cell||1 – 10 μM||Inhibited LPS induced IL-1b, IL-6, TNF-α, iNOS, COX- 2, PGE2. Inhibited activation of NF-κB, phosphorylation of ERK, JNK and p38 kinase87|
|Sauchinone||Roots||Microglial BV-2 cells and cultured astrocytes. Human osteoarthritis chondrocytes||1 – 10 μM
|Inhibited generation of ROS, NO, iNOS, COX-2, PGE2. Inhibited MMP-3 and MMP-13 release 88, 89 Inhibited β-secretase, STAT3, and NF- κB|
|Schisandrin B from Schisandra chinensis||Fruits||BV2 microglial cells. Human umbilical vein endothelial cells (HUVECs)||12.5 -50 μM
10 -40 μM
|Inhibited LPS induced TNF-α, IL-6, IL-1β,IL-8, ICAM-1, VCAM-1, and PGE2. Downregulated NF-κB upregulated the expression of PPAR-γ, Nrf2 and HO-1 90, 91|
|Schisandrin A||RAW 264.7 cells||50 -200 μM||Inhibited Lps induced NO and PGE2 by inhibiting iNOS and COX-2 respectively. Reduced TNF-α and IL-1β. Inhibited NF-κB, MAPK, and PI3K/Akt activity. Upregulated Nrf2 and HO-1 92|
|Schisandrin C||Human dental pulp cells (HDPC)||10 -20 μM||Inhibited LPS induced TNF-α, IL-1b, ICAM-1, VCAM-1.MMP-2 and -9, NO production, ROS formation, NF-κB. Upregulated SOD, HO-1, peroxisome proliferator-activated receptor-gamma coactivator 1-α, p-Akt and Nrf2 93|
|Gomisin N||Fruits||Human periodontal ligament cells (HPDLC). C57BL/6 mice: Attenuates Ethanol-Induced Hepatic Steatosis and Liver Injury SK-HEp-1 cells
20 mg/kg b.w.
|Inhibited TNF-α induced IL-6, IL-8, chemokine ligand CCL 2, and CCL20. Inhibited NF-κB, ERK and JNK pathway. Decreased MDA and CYP2E1 and increased SOD, catalase, GSH, and GPX levels. Enhances sirtuin1 (SIRT1) and phosphorylated AMP-kinase (AMPK)94, 95|
|Gomisin A||C57BL/6J peritoneal macrophages||0.01-1 ng/ml||Inhibited LPS induced COX-2, iNOS, IL-6, TNF-α and NO. Inhibited receptor-interacting protein 2 (RIP2) and NF-κB activity96|
|Taraxasterol from Taraxacum officinale||Aerial part and root||Wistar rats: suppressed Freunds Complete Adjuvant induced paw swelling and arthritis index, human umbilical vein endothelial cells||2-8 mg/kg b.w.
|Inhibited FCA/LPS induced TNF-α, IL-8, IL-1β, NO, iNOS, COX, PGE2, and RANKL, Increased serum OPG production. Decreased NF-κB and increased expression of LXRα97, 98|
|Triptolide from Tripterygium wilfordii||Leaves||BALB/c mice
Sprague Dawley rats
|5-15 μg/kg b.w.
|Reduced LPS/ TNF-α induced leukocyte, myeloperoxidase activity, edema of the lung,
Inhibited TNF-α, IL-1β, and IL-6, IL-8, iNOS, COX-2
Inhibited expression of TLR4 and NF-κB, ERK and JNK activity. Attenuated brain infarction volume, death of neuronal cells, Bcl2, Bax, caspase3 99-101
|Zingerone from Zinziber officinale||Rhizome||C57BL/6 mice
SW1353 cell line
|10-40 mg/kg b.w.
10-50 mg/kg b.w.
|Suppressed chemically induced BUN, creatinine, lactate dehydrogenase, and reduced inflammatory cytokines TNF-α, IL-6, IL-8, and IL-1 β. Inhibited TLR4, MyD88, TRIF expression and NF-κB, p38 and JNK activation 102-104|
|Gingerol||RAW264.7 cells||50-300 µg/ml||Inhibited LPS induced NO, PGE2, TNF-α, IL-1β, and IL-6. Inhibited iNOS and COX-2 mRNA expression. Inhibited NF-κB activation 105|
|6-Shogaol||BV2 microglial cells||Inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2. Inhibited NF-κB and increased PPAR-γ 106|
ADAMTS: disintegrin and metalloproteinase with thrombospondin motifs, Akt: Protein kinase B, AMPK: AMP-activated protein kinase, AP: activator protein, APP: Amyloid precursor protein, BACE: beta-site APP Cleaving Enzyme, BUN: blood urea nitrogen, CCL: chemokine ligand, CD: cluster of differentiation. COX-2: cycloxygenase2, CLP: cecal ligation and puncture, CXCL: chemokine (C-X-C motif) ligand, CYP: Cytochrome 450, DCFDA: 2',7'-dichlorodihydrofluorescein diacetate, Egr: early growth response proteins, ERβ: Estrogen receptor β, ERK: extracellular signal regulated kinase, GFAP: Glial fibrillary acidic protein, GMCSF: granulocyte macrophage colony stimulating factor, GSH: glutathione, GSK: glycogen synthase kinase, GR: glucocorticoid receptor, HO: heam oxygenase, IAP: Inhibitors of apoptosis proteins, ICAM: intercellular adhesion molecule, IFN: interferon, IKK: IκB kinase, IL: interleukin, iNOS: inducible nitric oxide synthase, IRAK: interleukin-1 receptor-associated kinase, JNK: Jun N terminal kinase, LPS: lipopolysaccharide, LXR: Liver X receptor, MadCAM: mucosal vascular addressin cell adhesion molecule, MAPK: mitogen activated protein kinase, MCP: monocyte chemoattractant protein, MD2: lymphocyte antigen 96, MDA: malondialdehyde, MIP: macrophage inflammatory protein, MMP: matrix metalloproteinase, Myd88: Myeloid differentiation primary response 88, NeuN: neuronal nuclei, Hexaribonucleotide Binding Protein, NF- κB: Nuclear factor kappa B, NLRP: Leucine rich Repeat and Pyrin domain containing, NO: nitric oxide, NOX: NADPH oxidase, Nrf: nuclear factor (erythroid derived), OCD/R: oxygen glucose deprivation and reoxygenation, OPG: osteoprotegerin, P21Waf1: Cip1/Kip1 family of cyclin-dependent kinase inhibitors, PECAM: platelet endothelial cell adhesion molecule, PGE2: Prostaglandin E2, PI3k: phosphatidylinositol 3-kinase,PKC: protein kianse C, PPAR: Peroxisome proliferator-activated receptor, PRDX: Peroxiredoxin, RIP: receptor interacting protein, ROS: Reactive oxygen species, RANKL: Receptor activator of nuclear factor kappa-Β ligand, SIRT: Sirtuin, SOD: superoxide dismutase, STAT: signal transducer and activator of transcription, TLR: toll like receptor, TBNS: 2,4,6-trinitrobenzene sulfonic acid, TNF: tumor necrosis factor, TP: thromboxane, TPA: 12-O-tetradecanoylphorbol- 13-acetate, TRAF: Tumor necrosis factor receptor–associated factor, TREM: Triggering receptor expressed on myeloid cells, VCAM: vascular cell adhesion molecule, VEGF: Vascular endothelial growth factor.
Mechanism of Action: The anti-inflammatory property of many of the active plant components was exhibited by their ability to bring down the common mediators of inflammation like NO, iNOS and pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, IL-12p40, etc. Chemokines such as RANTES, MCP-1, etc. were also inhibited by certain plant products. The other important mediators of inflammation such as cycloxygenase-2 (COX-2), prostaglandins and leukotrienes, the chosen targets of the existing anti-inflammatory drugs, were also downregulated by majority of compounds derived from plants. Reduction in ROS, lipid peroxidation along with upregulation of the enzymatic (superoxide dismutase, catalase, etc.) and non-enzymatic (glutathione, etc.) defense systems were also tested as markers of anti-inflammatory activity. Inhibition of neutrophil infiltration reduced expression of cell adhesion proteins (ICAM, VCAM, PECAM, etc.) and metallo-proteins (MMP-3, 8, 9, etc.) were also taken into account. All the above-mentioned events were mainly attributed to the downregulation of signaling pathways like NF- κB pathway by the naturally derived plant products. The MAP kinase pathway (p38, ERK, and JNK pathway) was also inhibited and Nrf2 pathway activated to bring about a remission of inflammation Table 1.
CONCLUSION: Therapies of inflammation must inhibit one or more of the pro-inflammatory mediators released from different cells without hampering the normal functions of the body. As the currently available drugs are yet to be perfected, researchers are looking into traditional and folk medicine in the pursuit of devising a more improved drug. The present study focuses on the role of traditional plants and their phytoconstituents in reducing inflammation along with their molecular mechanisms of action. Most of the plant's products exert their effect by reducing the known mediators of inflammation such as NO, TNF-α, IL-6, ROS, COX-2, and prostaglandins. These reductions were due to the inhibition of the signaling pathways like NF-κB pathway or MAP kinase pathways. This review attempts to present a collage of the different anti-inflammatory constituents from plants that would enable researchers to use this study as a foundation for their future experiments towards devising a more potent medicine for the treatment of inflammation.
ACKNOWLEDGEMENT: I hereby acknowledge my Ph.D. guide, Dept. of Pharmacology, IPGME & R, for introducing me to the field of medicinal plants with anti-inflammatory properties. I also acknowledge Officer in charge, Acharya Prafulla Chandra Roy Govt. College, and my departmental colleagues for giving me support to carry on my work.
CONFLICTS OF INTEREST: There are no conflicts of interest.
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How to cite this article:
Sarkar D: The anti-inflammatory activity of plant derived ingredients: an analytical review. Int J Pharm Sci & Res 2020; 11(2): 496-06. doi: 10.13040/IJPSR.0975-8232.11(2).496-06.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Department of Zoology, A.P.C. Roy Government College, Himanchal Vihar, Matigara, Siliguri, Darjeeling, West Bengal, India.
25 April 2019
06 August 2019
01 September 2019
01 February 2020