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Natural Painkillers

Varsha Rani, Nagendra Singh


Various natural sources are extensively used as traditional medicine for the management of various types of pain including tooth ache, gastric pain, abdominal pain, ear ache and generalized body pain. These natural painkillers are used as alternatives of synthetic painkillers which show adverse side effects in patients. They also possess long term antinociceptive, anti-inflammatory action in patient’s body. Various studies have been performed on a variety of natural sources possessing painkiller properties ex: turmeric (Curcuma longa), saffron, Isodon rugosus wall, clove, cobra venom, pista, Selaginella convoluta, alpinia galanga rhizome. Mostly the ethanolic and aqueous extract of these species possess both central and peripheral antinociceptive property to reduce pain.

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F. Halter, A. Tarnawski, A. Schmassmann, B. Peskar. Cyclooxygenase2implications on maintenance of gastricmucosal integrityandulcer healing:controversial issues and perspectives, Gut. 2001; 49: 443–53p. doi:10.1136/gut.49.3.443.

M.L. Lestari, G. Indrayanto. Curcumin. Profiles, Drug Subst Excip Relat Methodol. 2014; 39: 113–204p.

G.B. Mahady, S.L. Pendland, G. Yun, Z.Z. Lu. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen, Anticancer Res. 2002; 22: 4179–81p.

R.C. Reddy, P.G. Vatsala, V.G. Keshamouni, G. Padmanaban, P.N. Rangarajan. Curcumin for malaria therapy, Biochem Biophys Res Commun. 2005; 326: 472–4p.

L. Vera-Ramirez, P. Perez-Lopez, A. Varela-Lopez, M. Ramirez-Tortosa, M. Battino, J.L. Quiles. Curcumin and liver disease, Biofactors. 2013; 39: 88–100p.

L.E. Wright, J.B. Frye, B. Gorti, B.N. Timmermann, J.L. Funk. Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer, Curr Pharm Des. 2013; 19: 6218–25p.

B.B. Aggarwal, A. Kumar, A.C. Bharti. Anticancer potential of curcumin: preclinical and clinical studies, Anticancer Res. 2003; 23: 363–98p.

S.K. Sandur, M.K. Pandey, B. Sung, K.S. Ahn, A. Murakami, G. Sethi, P. Limtrakul, V. Badmaev, B.B. Aggarwal. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism, Carcinogenesis. 2007; 28: 1765–73p.

B. Joe, B.R. Lokesh. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages, Biochim Biophys Acta. 1994; 1224: 255–63p.

A.C. Reddy, B.R. Lokesh. Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats, Toxicology. 1996; 107: 39–45p.

R. Rukkumani, K. Aruna, P.S. Varma, V.P. Menon. Curcumin influences hepatic expression patterns of matrix metalloproteinases in liver toxicity, Ital J Biochem. 2004; 53: 61–6p.

B. Joe, M. Vijaykumar, B.R. Lokesh. Biological properties of curcumin-cellular and molecular mechanisms of action, Crit Rev Food Sci Nutr. 2004; 44: 97–111p.

B. Kocaadam, N. Sanlier. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health, Crit Rev Food Sci Nutr. 2015.

S. Reuter, S.C. Gupta, M.M. Chaturvedi, B.B. Aggarwal. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2014; 49: 1603–16p.

G. Sethi, B. Sung, B.B. Aggarwal. Nuclear factor-kappaB activation: from bench to bedside, Exp Biol Med. 2008; 233: 21–31p.

A. Anthwal, B.K. Thakur, M.S.M. Rawat, D.S. Rawat, A.K. Tyagi, B.B. Aggarwal. Synthesis, characterization and in vitro anticancer activity of C-5 curcumin analogues with potential to inhibit TNF-alpha-induced NF-kappaB activation, Bio Med Res Int. 2014.

S.C. Gupta, A.K. Tyagi, P. Deshmukh-Taskar, M. Hinojosa, S. Prasad, B.B. Aggarwal. Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols, Arch Biochem Biophys. 2014; 559: 91–9p.

E. Cretu, A. Trifan, A. Vasincu, A. Miron. Plant-derived anticancer agents – curcumin in cancer prevention and treatment, Rev Medico-Chir Soc Med Nat Iasi. 2012; 116: 1223–9p.

G. Ramadan, O. El-Menshawy. Protective effects of ginger-turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis, Int J Rheum Dis. 2013; 16: 219–29p.

P. Tyagi, H.A. Khan. Amelioration of oxidative stress in the joint tissue may be the basis for the antiarthritic activity of Terminalia arjuna bark extract, Int J Rheum Dis. 2014.

C. Park, D.O. Moon, I.W. Choi, B.T. Choi, T.J. Nam, C.H. Rhu, T.K. Kwon, W.H. Lee, G.Y. Kim, Y.H. Choi. Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis, Int J Mol Med. 2007; 20: 365–72p.

D.O. Moon, M.O. Kim, Y.H. Choi, Y.M. Park, G.Y. Kim. Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model, Int Immunopharmacol. 2010; 10: 605–10p.

M. Costigan, J. Scholz, C.J. Woolf. Neuropathic pain: a maladaptive response of the nervous system to damage, Annu Rev Neurosci. 2009; 32: 1–32p.

M. Zimmermann. Pathobiology of neuropathic pain, Eur J Pharmacol. 2001; 429: 23–37p.

D. Niv, M. Devor. Refractory neuropathic pain: the nature and extent of the problem, Pain Pract. 2006; 6: 3–9p.

S.H. Sindrup, T.S. Jensen. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action, Pain. 1999; 83: 389–400p.

R.N. Almeida, D.S. Navarro, J.M. Barbosa-Filho. Plants with central analgesic activity, Phytomedicine. 2008; 8: 310–22p.

P.A. Tarantilis, G. Tsoupras, M. Polissiou. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry, J Chromatogr A. 1995; 699: 107–18p.

J. Tavakkol-Afshari, A. Brook, S.H. Mousavi. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines, Food Chem Toxicol. 2008; 46: 3443–7p.

T. Ochiai, H. Shimeno, K. Mishima, K. Iwasaki, M. Fujiwara, H. Tanaka, Y. Shoyama, A. Toda, R. Eyanagi, S. Soeda. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo, Biochim Biophys Acta. 2007; 1770: 578–84p.

H. Hosseinzadeh, H.M. Younesi. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice, BMC Pharmacol. 2002; 2: 7p.

Y. Zhu, T. Han, Q.Y. Zhang, L.P. Qin. The comparative studies on the analgesic and anti-inflammatory activities of different parts from Crocus sativus, J Pharm Pract. 2008; 4: 269–71p.

G.J. Bennett, Y.K. Xie. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man, Pain. 1998; 33: 87–107p.

H. Ali Safakhah, T. Taghavi, A. Rashidy-Pour, A.A. Vafaei, M. Sokhanvar, N. Mohebbi, M. Rezaei-Tavirani. Effects of saffron (Crocus sativus L.) stigma extract and its active constituent crocin on neuropathic pain responses in a rat model of chronic constriction injury, Iran J Pharm Res. 2016; 15(1): 253–61p.

S.Y. He, Z.Y. Qian, F.T. Tang. Effect of crocin on intracellular calcium concentration in cultured bovine aortic smooth muscle cells, Yao Xue Xue Bao. 2004; 39: 778–81p.

B.A. Williams, C. Liu, L. Deyoung, G.B. Brock, S.M. Sims. Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and Cgmp, Am J Physiol Cell Physiol. 2005; 288: C650–8p.

M. Starec, D. Waitzová, J. Elis. [Evaluation of the analgesic effect of RG-tannin using the «hot plate» and «tail flick» method in mice], Cesk Farm. 1988; 37: 319–21p.

S. Ma, S. Zhou, B. Shu, J. Zhou. Pharmacological studies on Crocus glycosides I. Effects on anti-inflammatory and immune function, Zhongcaoyao. 1998; 29: 536–9p.

M. Shuaib, I. Khan. Study of medicinal plants of lower Dir, Timergara, Tehsil Balambat, Khyber Paktunkhaw-Pakistan, Am Eurasian J Agric Environ Sci. 2015; 15: 2088–94p. doi: 10.5829/idosi. aejaes. 2015.15.10.12811.

M. Sabeen, S.S. Ahmad. Exploring the folk medicinal flora of Abbotabad city, Pakistan, Ethnobot Leaflets 2009; 13: 810–33p.

M. Ahmad, S. Sultana, S. Fazl-I-Hadi, T. BenHadda, S. Rashid, M. Zafar, et al. An ethno botanica lstudy of medicinal plants in high mountainous region of Chailvalley (DistrictSwat-Pakistan), J Ethnobiol Ethnomed. 2014. 10:36. doi:10.1186/1746-4269-10-36p.

A. Zeb, S. Ahmad, F. Ullah, M. Ayaz, A. Sadiq. Antinociceptive activity of ethnomedicinally important analgesic plant Isodonrugosus Wall. exBenth: mechanistic study and identifications of bioactive compounds, Front Pharmacol. 2016; 7: 200p. doi: 10.3389/fphar.2016.00200.

A.N. Daniel, S.M. Sartoretto, G. Schmidt, S.M. Caparroz-Assef, C.A. Bersani-Amado, R.K.N. Cuman. Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models, Rev Bras Farmacogn. 2009; 19: 212–7p.

E.T. Arung, E. Matsubara, I.W. Kusuma, E. Sukaton, K. Shimizu, R. Kondo. Inhibitory components from the buds of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells, Fitoterapia. 2011; 82: 198–202p.

H.A. Elwakeel, H.A. Moneim, M. Farid, A.A. Gohar. Clove oil cream: a new effective treatment for chronic anal fissure, Colorectal Dis. 2007; 9: 549–52p.

M.K. Asl, A. Nazariborun, M. Hosseini. Analgesic effect of the aqueous and ethanolic extracts of clove, Avicenn J Phytomed. 186–92p.

A.N. Daniel, S.M. Sartoretto, G. Schmidt, S.M. Caparroz-Assef, C.A. Bersani-Amado, R.K.N. Cuman. Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models, Rev Bras Farmacogn. 2009; 19: 212–7p.

R. Kurian, D.K. Arulmozhi, A. Veeranjaneyulu, S.L. Bodhankar.Effect of eugenol on animal models of nociception, Indian J Pharmacol. 2006; 38: 341–5p.

A. Ozturk, H. Ozbek. The anti-inflammatory activity of Eugenia caryophyllata essential oil: an animal model of anti-inflammatory activity, Eur J Gen Med. 2005; 2: 159–63p.

H. Raghavenra, B.T. Diwakr, B.R. Lokesh, K.A. Naidu. Eugenol – the active principle from cloves inhibits 5-lipoxygenase activity and leukotriene-C4 in human PMNL cells, Prostaglandin Leukot Essent Fatty Acids. 2006; 74: 23–7p.

S. Halder, A.K. Mehta, P.K. Mediratta, K.K. Sharma. Acute effect of essential oil of Eugenia caryophyllata on cognition and pain in mice, Naunyn Schmiedebergs Arch Pharmacol. 2012; 385: 587–93p.

J. Feng, J.M. Lipton. Eugenol: antipyretic activity in rabbits, Neuropharmacology. 1987; 26: 1775–8p.

Y. Murakami, M. Shoji, S. Hanazawa, S. Tanaka, S. Fujisawa. Preventive effect of biseugenol, a eugenol ortho dimer, on lipopolysaccharide-stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages, Biochem Pharmacol. 2003; 66: 1061–6p.

G. Kozam. The effect of eugenol on nerve transmission, Oral Surg Oral Med Oral Pathol. 1977; 44: 799–805p.

S.A. Guenette, A. Ross, J.F. Marier, F. Beaudry, P. Vachon. Pharmacokinetics of eugenol and its effects on thermal hypersensitivity in rats, Eur J Pharmacol. 2007; 562: 60–7p.

H. Aoshima, K. Hamamoto. Potentiation of GABAA receptors expressed in Xenopus oocytes by perfume and phytoncid, Biosci Biotechnol Biochem. 1999; 63: 743–8p.

C. Ghelardini, N. Galeotti, L. Di Cesare Mannelli, G. Mazzanti, A. Bartolini. Local anaesthetic activity of [beta]-caryophyllene, Il Farmaco. 2001; 56: 387–9p.

S.H. Park, Y.B. Sim, J.K. Lee, S.M. Kim, Y.J. Kang, J.S. Jung, H.W. Suh. The analgesic effects and mechanisms of orally administered eugenol, Arch Pharm Res. 2011b; 34: 501–7p.

E. Grasset. The cobra neurotoxin; pharmacology and clinical applications in the treatment of pain, Med Hyg (Geneve). 1952; 10: 55–8p.

R.J. Lukas. Diversity and patterns of regulation of nicotinic receptor subtypes, Ann NY Acad Sci. 1955; 757: 153–8p.

D. Servent, S. Anti-Delbeke, C. Gaillard, P.J. Corringer, J.P. Changeux, A. Menenz. Molecular characterization of the specificity of interactions of various neurotoxins on two distinct nicotinic acetylcholine receptors, Eur J Pharmacol. 2000; 393: 197–204p.

F. Dajas-Bailador, G. Costa, F. Dajas, S. Emmett. Effects of α- bungarotoxin, α-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo, Neurochem Int. 1998; 33: 307–12p.

C. Lena, J.P. Changeux. Role of Ca2+ ions in nicotinic facilitation of GABA release in mouse thalamus, J Neurosci. 1997; 17: 576–85p.

Z.-x. Chen, H.-l. Zhang, Z.-l. Gu, B.-w. Chen, R. Han, P.F. Reid, L.N. Raymond, Z.-h. Qin. A long-form α-neurotoxin from cobra venom produces potent opioid independent analgesia, doi: 10.1111/j.1745-7254.2006.00293.x.

H.R. Mundy, S.J. Jones, J.C. Hobart, M.G. Hanna, P.J. Lee. A randomized controlled study of modified cobratoxin in adreno myelo neuropathy, Neurology. 2003; 61: 528–30p.

W.C. Evans. Trease and Evans Pharmacognosy. University of Nottingham, Nottingham 471, 2002.

E.M. Giner-Larza, S. Máñez, M.C. Recio, R.M. Giner, J.M. Prieto, M. Cerdá-Nicolás, J.L. Ríos. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity, Eur J Pharmacol. 2001; 428: 137–43p.

H. Hosseinzadeh, M. Mirshojaeian, B.M. Razavi. Antiemetic effect of Pistacia vera L (2008). (Pistachio) leaves and nuts aqueous extracts in young chicken, Pharmacologyonline. 2008; 2: 568–71p.

S.N.M. Parvardeh, A.M. Nassiri, H. Hosseinzadeh. Antinociceptive, anti-inflammatory and acute toxicity effects of Pistacia Vera L. gum extract in mice and rats, J Med Plants. 2002; 4: 59–68p.

S.N.M. Parvardeh, H. Hosseinzadeh. Hepatoprotective activity of Pistacia Vera L. gum extract in rats, J Med Plants. 2002; 4: 27–34p.

E.M. Giner-Larza, S. Máñez, M.C. Recio, R.M. Giner, J.M. Prieto, M. Cerdá-Nicolás, J.L. Ríos. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity, Eur J Pharmacol. 2001; 428: 137–43p.

H. Hosseinzadeh, E. Behravan, M.M. Soleimani. Antinociceptive and anti-inflammatory effects of Pistacia vera leaf extract in mice, Iran J Pharm Res. 2011; 10(4): 821–8p.

S.H. Ansari, M. Ali, J.Q. Qadry. New tetracyclic triterpenoids from Pistacia integerrima galls, Pharmazie. 1994; 49: 356–7p.

P. Guilherme S de Sá, X.P. Nunes, J.T. de Lima, J.A. de Siqueira Filho, A.P. Fontana, J. de Souza Siqueira, L.J. Quintans-Júnior, P.K. Fonseca Damasceno, C.R. Cardoso Branco, A. Branco, J.R. Guedes da Silva Almeida. Antinociceptive effect of ethanolic extract of Selaginella convoluta in mice, BMC Complement Alternat Med. 2012; 12: 187p.

P. Clavelou, R. Dallel, T. Orliaguet, A. Woda, P. Raboisson. The orofacial formalin test in rats: effects of different formalin concentrations, Pain. 62: 295–301p.

M.G.D. Melo, A.A.S. Araújo, C.P.L. Rocha, E.M.S.A. Almeida, R.S. Siqueira, L.R. Bonjardim, L.J. Quintans-Júnior. Purification, physicochemical properties, thermal analysis and antinociceptive effect of atranorin extracted from Cladina kalbi, Biol Pharm Bull. 2008; 31: 1977–80p.

E. Middleton, C. Kandaswami, T.C. Theoharides. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer, Pharmacol Rev. 2000; 52: 673–751p.

S.D. Acharya, S.D. Ullal, S. Padiyar, Y.D. Rao, K. Upadhyaya, D. Pillai, V. Raj. Analgesic effect of extracts of Alpinia galangal rhizome in mice, J Chin Integr Med. 2011; 9(1): 100–4p.

E.R. Almeida, R.N. Almeida, D.S. Navarro, J. Bhattacharryya, B.A. Silva. Central antinociceptive effect of a hydroalcoholic extract of Dioclea grandi flora seeds in rodents, J Ethnopharmacol. 2003; 88(1): 1–4p.

F.A. Santos, V.S. Rao. Antiinflammatory and antinociceptive effects of 1, 8-cineole a terpenoid oxide present in many plant essential oils, Phytother Res. 2000; 14(4): 240–4p.


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