ETHANOMEDICINAL PLANTS WITH ANTI-INFLAMMATORY EFFECT FROM SOUTHERN HARYANA, INDIA: A REVIEW

Inflammation is a physiological host response to external challenges or cellular injury such as pathogens, damaged cells or irritants leading to the release of a complex array of inflammatory mediators and aiding the recovery of tissue structure and function.All inflammatory processes develop along a known sequence: locally increased blood supply, leakage of fluid, small molecule or proteins and infiltration of cells.Inflammation is not a synonym for infection, even in case where inflammation is caused by infection, response includes clinical signs of erythema, edema, hyperalgesia and pain. Since the ancient Greek and Roman era five basic symptoms of inflammation have been known i.e, redness, swelling, heat, pain and deranged function are produced by inflammatory agents such as nitric oxide, prostaglandins, bradykinin, serotonin, leukotrienes and histamine. The inflammatory process is a series of events that can be elicited by numerous stimuli such as infectious and thermal or physical injury through years of ingenious synthesis and structural modifications.

There are various medicines for controlling and suppressing inflammatory crisis; steroids, nonsteroid antiinflammatory drugs and immunosuppressant are the practical examples of these medications which are associated with adverse effects (Ghasemian, et al., 2016). Thus, we need to apply natural anti-inflammatory factors within medication therapy to achieve increased pharmacological response and the lowest degree of unwanted side effects (Bagad et al., 2013;Sowemimo et al., 2013;Ghasemian, et al., 2015). The use of traditional medicine is expanding to new horizons and plants still remained as the novel source of structurally important compounds that lead to the development of novel drugs. Herbal medicines are promoting subjects in medicine and, of course, we have to increase our knowledge about them. In this review, we have endeavored to assess the role of plant metabolities in inflammation and plants from Southern Haryana reported traditionally or clinically for their anti-inflammatory effects.

Role of plant metabolites in inflammation:
Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Many substances which interfere with the inflammatory response have been isolated from plants/herbs. Traditionally, people have been using powerful anti-inflammatory plants for thousands of years. Plants secondary metabolites have provided an important source of drugs since ancient times and now around half of the practical drugs used are derived from natural sources (Wang et al., 2008) and many of these herbal constituents are being prescribed widely for the treatment of inflammatory conditions (Bagul et al., 2005).

Phenolic compounds:
Phenolic compounds includes flavonoids, coumarins, tannins and phenolic acid are of important pharmacological value, some having anti-inflammatory properties (Yoon and Baek 2005; Mukherjee and Houghton 2009). Different types of phenolics compounds such as flavonoids, condensed tannins, and gallotannins are known to inhibit some molecular targets of pro-inflammatory mediators in inflammatory responses (Wadah et al., 2014;Fawole et al., 2009;Phanse et al., 2012).

Tannins and phenolic acids:
Condensed tannins (proanthocyanidins) are essentially derived from [+] gallocatechin, [−] epicatechin, [+] catechin and epigallocatechin, and their derivatives via carbon to carbon (C-C) links (Fawole et al., 2009;Agrawal and Paridhavi 2007). Proanthocyanidins are naturally-occurring plant metabolites, widely available in fruits, vegetables, nuts, seeds, flowers and bark. The beneficial effects of proanthocyanidins on human health have been attributed mainly to their strong free radical-scavenging and antioxidant activities. Proanthocyanidins are also associated with a number of biological activities, such as anti-inflammatory, anti-asthmatic, anticancer, antimicrobial, anti-allergy, antihypertensive and cardioprotective. (Diouf et al., 2009). These compounds are antagonists of particular hormone receptors or inhibitors of particular enzymes such as Cyclooxygenase (COX) enzymes (Agrawal and Paridhavi 2007). Gallotannins exert anti-inflammatory properties due to scavenging of radicals (Mangathayaru 2013) and inhibition of the expression of inflammatory mediators, such as some cytokines, inducible nitric-oxide synthase (iNOS), and COX-2 (Fawole et al., 2009. It has been reported that some caffetannins and related compounds inhibit 5-Hydroxyeicosatetraenoic acid(HETE) and 5-lipooxygenase production, whereas others such as caffeic acid and caffeoylmalic acid have been reported to enhance Prostaglandin E 2 (PGE2) formation in a concentration-dependent fashion (Kimura et al., 1987).

Flavonoids:
Flavonoids are an important group of low molecular secondary metabolites produced by plants. They are polyphenolic compounds (Wadah et al., 2014;Mangathayaru 2013) naturally occurring in vegetables, fruits, flowers, seeds, grain, bark, stems, roots etc. Over 4000 different flavonoids have been described, and they are categorized into flavonols, flavones, catechins, flavanones, anthocyanidins and isoflavonoids (Wadah et al., 2014;Tandon and Verma 2009). Flavonoids have a variety of biological effects. they have been shown antimicrobial, antiviral, antiulcerogenic, cytotoxic, antineoplastic, mutagenic, anti-inflammatory, antioxidant, antihepatotoxic, antihipertensive, hypolipidemic and antiplatelet activities (Wadah et al., 2014;Mangathayaru 2013;Guabiraba et al., 2010).Flavonoids are known to act on the inflammatory response via many routes and blockmolecules like cyclooxygenease,inducible nitric-oxide synthase, cytokines, nuclear factor-кB and matrix metalloproeinases (Fawole et al., 2009).Flavonoids are rapidly absorbed by the human body and have been reported to have positive effects on numerous aspects of health, including a reduced risk of coronary heart disease, cancer, neurodegenerative diseases (Stough and Scholey 2013). Flavonoids showed significant activity in both proliferative and exudative phases of inflammation in rat models of inflammation. Flavonoids (such as rutin, quercetin, hesperidin) showed antiinflammatory activity and inhibited the development of the induced granuloma (Guabiraba et al., 2010;Guardia et al., 2001). Some flavonoids, such as quercetin, blocked both the cyclooxygenase and lipooxygenase pathways at relatively high concentrations, while at lower concentrations; the lipooxygenase pathway was the primary target of inhibitory anti-inflammatory activity. On the other hand, when administered subcutaneously, hesperidin [hesperetin-7-rutinoside] exhibited significant anti-inflammatory activity on rat paw edema induced by both carrageenan and dextran and on carrageenan pleurisy, without producing the side effects that are caused by other classes of antiinflammatory drugs (Guabiraba et al., 2010).

Coumarins:
Coumarins represent a vast family of compounds which were naturally found in plants (Wadah et al., 2014). Several coumarins have been reported that possess anti-inflammatory activity. Aesculetin and scopolin isolated from Santolina oblongifolia show marked activity as inhibitors of release of eicosanoids (Silvan et al., 1996). Coumarin derivatives could be particularly effective in the treatment of high protein oedemas. It was reported that some coumarins possessed the antioxidant capacity scavenging superoxide anion radicals and some coumarins could 1016

Alkaloids:
Alkaloids are a chemically heterogenous group of basic nitrogen containing substances found predominately in higher plants (Bhat et al., 2010). They have great diversity in their botanical and biochemical origin in chemical structure and pharmacological activity (Mangathayaru 2013) has also showed anti-inflammatory and analgesic activities . They also inhibited inflammatory mediators, capillary permeability, vasodilation, free radicals formation, platelets aggregation, endothelial derived factors and intracellular pro-inflammatory mediators.
In additions alkaloids' able to restore body defense mechanisms by augmenting antioxidants and other associated biomolecules Bhat et al., 2010). Some alkaloids such as isoquinoline, indole and diterpene are known to have good anti-inflammatory activity (Mangathayaru 2013). Recently, there has been interest in the use of bisbenzylisoquinoline alkaloids as potential antiinflammatory drugs, based on their ability to prevent the synthesis or the action of some proinflammatory cytokines. Some antirheumatic remedies in East medicine have been using bisbenzylisoquinoline alkaloids as major components since antiquity .They also possess antiinflammatory, immunomodulatory and antimalarial activities. One of the most investigated bisbenzylisoquinoline alkaloids is tetrandrine and its analogues berbamine and fangchinoline (Satoh et al., 2003). Bisbenzylisoquinoline alkaloids exhibited suppressive effects on in vitro histamine release and nitric oxide production. Cepharanthine was a highly potent inhibitor of HIV-replication in chronically infected monocytic cell line and suppressed the production of inflammatory cytokines and neural cell death (Wadah et al., 2014).

Terpenes:
The The anti-atherogenic effects may be due, not only to their cholesterol-lowering activities, but also to other properties, such as effects on the coagulation system, an antioxidant system, and hepatic and lipoprotein lipase activities. Humans are not able to synthesize phytosterols, and dietary consumption is the only source of these 1017 compounds (Haiyin He et al., 1995). Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects (Aldini et al., 2014).Phytosterols and phytostanols are plant derived sterols, structurally related to cholesterol (Ostlund 2002). Guggulsterone suppresses NF-kappaB and NF-kappaB-regulated gene products, which may explain its antiinflammatory activities (Shishodia and Aggarwal 2004).

Medicinal plants with anti-inflammatory activity from Southern Haryana:
Haryana state is rich in plant biodiversity and provides habitat for a significant number of medicinal plants. Districts of South Haryana consist of Gurgaon district, Mahendragarh district, Palwal district and Rewari district. Literature survey on medicinal plant from southern Haryana were reavaled many medicinal plants which has shown antiinflammatory activities, some of them are listed in table 1 shown below: Chief constitutents are alkaloidal amines (0.5-2%). Important alkaloids are lepherdrine, d-pseudoephedrine, 1-methyl ephedrine, non-ephedrine and dimethyl ephedrine and adrenaline.
Ephedrine increases blood pressure so it is used in asthma, hay fever, and whooping cough. It is cardiac and respiratory stimulant. 35 Erythroxylum coca Lam. Family: Erythroxylaceae Common name: Cocoa It is a source of cocaine alkaloid (coke) one of the oldest anaesthetic and a highly addictive narcotic, causing indifference to pain and tiredness. 36 Eugenia caryophyllus L. Family: Myrtaceae Common name: Clove, lavang The Essential oil, eugenol is antiseptic and analgesic. The eugenol oil is composed of acetyl eugenol, Methyl salicylate, pinene and vanillin.
The oil is an excellent nerve pain drug and is therefore used To relieve tooth ache and muscle spasm. Routinely used in dentistry for centuries, it is an essential component of many types of toothpaste and also used as a flavouring agent. 37 Gelsimiun sempervirens (L.) J. St. Hil family : Logoniaceae common name: Yellow jasmine The roots contain yellow jasmine indole alkaloid (gelsemine and gelsedine), iridoids, coumarins etc.
Used as a sedative, and commonly used in neuralgia migraine. It is also used as an antispasmodic and for suicidal patients. 38 Glycyrrhiza glabra L. family: Fabaceae common name: Yashtimadhu, liquorice They contain the active constituents, glycyrrhizin, sugar, resign, phytoestrogen and flavonoids.
The antiinflammatory principle is derived from glycyrrhic acid, which gets converted to glycyrrhetic acid. 39 Harpagophytum procumbens DC Family: Pedaliaceae common name: Devil's claw, grapple apple The active chemical constituents are iridoid glycosides (harpagoside), stachyose sugars, phytosterols, flavonoids and harpagoquinone. The plant is a good anti-inflammatory and analgesic agent that relieves joint pain/rheumatism anti-inflammatory, exudative and analgesic properties of this plant in easing joint pains, and muscular problems 40 Hemidesmus indicus (L.) Sm. Family: Asclepidaceae (zingiberine and bisabolene), apart from gingerol, gingren oils, methylgingediol, gingeryl and methyl gingediacetates.
The activity is due to gingerol, Dehydrogingeridion e and gingerdione were shown to be potent inhibitors of prostaglandin synthesis which confirms the mechanism of antiinflammatory and antirheumatic effects.