REVIEW ARTICLE: ANALGESIC ACTIVITY OF A POTENTIAL SOURCE OF MODERN MEDICINE
HTML Full TextREVIEW ARTICLE: ANALGESIC ACTIVITY OF A POTENTIAL SOURCE OF MODERN MEDICINE
Amrita Asthana and Neeraj Sharma
Department of Pharmacy, Bhagwant University, Rajasthan Sikar Rode, Ajmer, Rajasthan, India.
ABSTRACT: Recently, scientific investigations of medicinal plants using indigenous medical systems have attracted a lot of attention in international investigation. Nature has imparted our planet with an enormous wealth of medicinal plants known for bestowing and are highly esteemed worldwide as a rich source of therapeutic agents for the prevention and cure of diseases and ailments. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Herbal drugs can be potential drugs to replace them. Every year, many plants from the traditional medicinal system may be screened for their potential analgesic activity. Still, only a few of them only included in the health care system after clinical research. So this is time to give more emphasis on research work based on natural sources, investigate the active phytochemical constituents, and use them on a specific treatment.
Keywords: Herbal druds, Phytoconstituents, Analgesic
INTRODUCTION: Plants have been important and basic of preventive and curative health care systems since ancient times. The disease is as old as mankind, and indigenous herbal medicines are a very ancient art and an entire part of treatment 1. Traditional medicinal herbs have served as a potential source of alternative medicine and different healthcare products. From immemorial time Indian, Chinese, Egyptian, Greek, Roman, and Syrian medicinal system documented the use of different plant-based medicine for different diseases 2. According to WHO, approximately 75-80% of the world population still depends on herbal medication.
Active chemical constituents from plant sources directly used as therapeutic agents and phytoconstituents are also provided as lead molecules for synthesizing various drugs 2, 3. Folk medicine and its use against diseases in different cultures are a vast traditional knowledge based on the necessities, instinct, aim, trial and error, and long experience of immemorial/tribal people 4. Ayurveda is used to treat inflammation, anaemia, asthma, blood disorders, bronchitis, fever, urinary infection, and splenomegaly diseases 5.
Pain- Pain is a heterogenous phenomenon that accompanies the body's inflammatory response to tissue damage. The immune cells at the injury site actively release chemical mediators that result in vasodilatation, increased vascular permeability, and cellular infiltration 6. The mechanism is conducive to scavenging necrotic tissue and promoting tissue healing. Pain is rightly defined as a: complex constellation of unpleasant sensory, emotional and cognitive experiences provoked by real or perceived tissue damage and manifested by certain autonomic, psychological and behavioural reactions 7. Inhibitory and excitatory pathways modulate the sensory and affective components of pain. Inhibitory neurotransmitters (noradrenaline and serotonin) and drugs (clonidine and dexmedetomidine) act as agonists on α2 adrenoceptors in dorsal horn cells of the spinal cord causing supraspinal analgesia 8. The latest research has shown that non-steroidal anti-inflammatory drugs (NSAIDS) also facilitate noradrenergic activation of α1, α2C, and β-adrenoceptors in addition to their peripheral anti-nociceptive action 9. COX inhibitors are an integral part of most analgesic actions. COX enzymes are in two forms, COX-1 and COX-2. COX-1 is constitutive and produces prostanoids essential for physiological processes, including the protection of gastric mucosa. COX-2 is inducible and synthesizes prostanoids that mediate inflammatory actions like pain, fever, tissue injury, and infection. Classic NSAIDs inhibit COX-1 and COX-2 and decrease pain in acute and chronic pain conditions across the entire spectrum of pain severity 10. However, non-selective inhibition of COX interferes with physiological actions and causes adverse effects like peptic ulcers, platelet dysfunction, helicobacter pylori infection, and nephrotoxicity.
On the other hand, COX-2 inhibitors exhibit fewer gastrointestinal and other side effects but have similar anti-inflammatory, anti-pyretic, and analgesic properties 11. In inflammatory states, the expression of COX-2 is accentuated centrally and peripherally under the proinflammatory cytokine IL-1-b. COX-2 inhibitors modulate nociception through differential activity at both sites 11. Zaltoprofen, a preferential COX-2 inhibitor, is a potent anti-inflammatory and analgesic propionic acid derivative with novel anti-nociceptive properties. It decreases PGE2 production by acting at the COX enzyme and inhibits the bradykinin and lipoxygenase pathway of nociception.12 The B2 receptor-mediated signaling pathway on the primary sensory neurons is attenuated without actual blocking of bradykinin receptors. It has a greater inhibitory effect on bradykinin-induced nociception than other NSAIDs.
Types of pain:
Somatic Pain: caused by the activation of pain receptors in either the body surface, which causes likes abnormalities, inflammation, repetitive trauma, excessive activity, vigorous stretching, and contractions due to paralysis.
Visceral Pain: It is associated with the damage of internal organs and is the most common form of pain, resulting from the activation of pain receptors in the chest, abdomen, and pelvic areas.
Neuropathic Pain: it is caused by injury or malfunction to the spinal cord and peripheral nerves associated with burning, tingling, shooting, stinging, pins and needles.
Acute Pain: acute pain is associated with tissue damage or injury, but usually goes away as the injury heals or the cause of the pain is short-lasting and usually manifests in ways that could be easily described and observed.
Chronic Pain: pain lasting for more than three months and more subjective; treating chronic pain poses a great challenge for physicians as it can change the function and quality of life.
TABLE 1: SOME OF THE COMMONLY USED ANALGESIC DRUGS AND THEIR ADVERSE EFFECT 13, 14, 15
S. no. | Drug | Adverse Effect |
1. | Fentanyl | sedation, sweating, headache, vertigo, lethargy, confusion, light-headedness, nausea, vomiting, respiratory depression |
2. | Codeine | sedation, sweating, headache, dizziness, lethargy, confusion, light-headedness |
3. | Methadone | light-headedness, dizziness, constipation, respiratory depression, sedation, nausea, vomiting, physical dependence |
4. | Morphine sulfate | sedation, hypotension, increased sweating, constipation, dizziness, drowsiness, nausea, vomiting, dry mouth, somnolence, respiratory depression due to acute opioid poisoning, dysphoria |
5. | Pentazocine | light-headedness, sedation, constipation, dizziness, nausea, vomiting, respiratory depression, and high doses increase blood pressure and can cause hallucinations, nightmares, dysphoria, tachycardia, dizziness |
6. | Buprenorphine | light-headedness, sedation, constipation, dizziness, nausea, vomiting, respiratory depression |
TABLE 2: SOME OF PLANT SOURCE WITH ANALGESIC ACTIVITY 16 -26
S. no. | Botanical Name (Common Name) Family | Part used | Chemical Constituent | Activity |
1. | Sterculia foetida (Jangli badam) Sterculiaceae | seeds | Fat, cycloprenoid fatty acids. | Antiinflammatory, Analgesics |
2. | Tridex procumbens (Ghamra) Asteraceae |
leaves |
flavonoids, procumbentin and quercetin, βsitosterol | Antiinflammatory, Analgesics |
3. | Cissus rependa (Panibel) Vitaceae | Root, Stem | Alkaloids, glycosides, saponins, tannins. | Antiinflammatory, Analgesic |
4. | Hedyotis puberula (Surbuli) Rubiaceae | whole plant | Iridoid glycosides | Antiinflammatory, Analgesics |
5. | Eucalyptus citriodora (lemon eucalyptus) Myrtaceae | essential oil | Terpenes, alkaloids, flavonoids, tannins, eucalyptol. | Antiinflammatory, Analgesics |
6. | Chococca brachiata Rubiaceae | Root | Steroids, phenolic compounds, ligans | Antiinflammatory, Analgesics |
7. | Tanacetum artemisioides (Paloyo Zoon) | whole plant | Asteraceae Flavonoids | Antiinflammatory, Analgesics |
8. | Kaempferia galangal (Aromatic ginger) (Zingiberaceae) | fresh rhizome | ethyl-p-methoxycinnamate, methylcinnamate, Carvone, etc | Antiinflammatory, Analgesics |
9. | Clerodendrum phlomidis (Arni) Verbenaceae | Stem bark | Alkaloids, glycosides, saponins, tannins | Analgesic |
10. | 31 Cynara scolymus (Globe artichoke ) Asteraceae | Leaves | Sesquiterpenes, flavone glycosides, volatile oil. | Antiinflammatory, Analgesics |
11. | Elephantopus scaber (Elephant foot) Asteraceae | Leaves | Glycosides, stigmasterol, deoxyelephantopin | Antiinflammatory, Analgesics |
12. | Bauhinia racemosa (Kachnal) Caesalpiniaceae | Stem bark | Flavonoids, saponins, glycosides, tannins | Analgesic |
13. | Mikania glomerata (sprengel) Asteraceae | Leaves | Coumarins. | Antiinflammatory, Analgesics |
14. | Sida acuta (Bariara) Malvaceae | whole plant | alkaloids, flavanoids, steroids, tannins, terpenoids | Analgesic |
15. | Toona celiata (Tun) Meliaceae | Heartwood | Phytosterols, coumarins, carbohydrates. | Analgesic |
16. | Baugainvilla spectabillis (Booganbel) Nyctaginaceae | Leaves | flavanoids, Alkaloids, tannins, betacyanine, pinitol. | Analgesic |
17. | Ficus glomerata (Cluster Fig Tree) Moraceae | Bark and leaves | Betasitosterol, lupeol, stigmasterol, leucoanthocyanins. | Analgesic |
18. | Polyalthia longifolia (Devadaru) Annonaceae | Leaves | Diterpenes, alkaloids. | Analgesic |
19. | Tridax procumbens (Tridax daisy) Compositae | leaves | Saponins, Alkaloids, Flavanoids, Proteins, Phytosterols, | Analgesic |
Alkaloid as Analgesic Used as Medicinal Plants: Crude alkaloids of medicinal plants showed famous analgesic potentials through inhibition of peripheral and central nervous system mechanisms. Further work is required for the isolation of the pharmacologically active constituents. These analgesic activities are associated with many adverse effects like intoxication, which cause physical dependence, tolerance, and addiction. NSAIDs are repeatedly associated with gastrointestinal disorders like gastric or duodenal ulceration 27. This obligates the discovery of relatively safe alternatives for pain treatment. Medicinal herbs have been used for therapeutic purposes for centuries. Many of these herbs has been used for pain management without any evident adverse effects 28. Ethno-pharmacologically guided research has brought considerable contributions to new drug development 29, 30. There was an increasing interest in finding new and safe anti-inflammatory and analgesic drugs from natural sources, including medicinal plants 31. Medicinal plants had been a very useful source of lead structure for subsequent synthetic modification and optimization of bioactivity. Alkaloids are naturally occurring active, diverse groups of secondary metabolites in plants that have been used in medicine for hundreds of years 32. Plants like Woodfordia fruticosa, Adhatoda vasica, Chenopodium ambrosioides, Viburnum cotinifolium, Vitex negundo, Peganum harmala and Broussonetia papyrifera have been investigated scientifically for the presence of alkaloids regarding their ethnopharmacological profile in pain management 33, 34, 35. Analgesic activity of alkaloids isolated from plants is reported with different mechanistic approaches 36, 37. The strong positive correlation of alkaloids in medicinal plants for analgesic activity persuades an intent to determine the possible analgesic activity of total alkaloids extracted from the mentioned medicinal plants using animals’ model. Pain management sometimes requires more than one drug therapy. Thus the practice of polypharmacy carries risks of adverse drug reactions and side effects. Therefore, the search for new drugs with the same therapeutic impact with relatively less frequency of side effects is the need of the time 38, 39.
This study helped us understand the possible mechanisms of potential analgesic effects of the test alkaloids that work through inhibition of the central nervous system and peripheral nervous system. The abdominal constriction induced by acetic acid is thought to be due to the involvement of peripheral mechanisms. In contrast, tail immersion test model testing of analgesic activity thought to be due to central mechanisms 40. Formalin test is used for both peripheral and central mechanisms 41. The formalin test model is used to investigate the ability to draw peripheral and/ or central analgesic effects as it assays biphasic characteristics, labeled as the early and late phases resulting from formalin administration 42. The early phases are neurogenic pain resulting from an acute response toward direct action of formalin on nociceptors within the intraplantar region. In contrast, the late phase is considered an inflammatory-mediated pain resulting from a tonic response due to the release of inflammatory mediators 43. The crude alkaloidal extracts of different medicinal plants get analgesic potentials, possibly through inhibition of central and peripheral pain mediators. The antinociceptive activity confirms traditional uses of the aforesaid medicinal plants for pain management.
CONCLUSION: State-of-the-art clinical intervention studies, that is, randomized, double-blind placebo-controlled trials, are the gold standard for testing whether a substance has a therapeutical or preventive potential; this research area often suffers from either inadequately performed or a low number of studies. In this minireview, we did try not only to pinpoint deficiencies but also to highlight positive developments that will be bright and advance disease prevention or therapy.
ACKNOWLEDGEMENT: Nil
CONFLICTS OF INTEREST: Nil
REFERENCES:
- Sen S, Chakraborty R, Sridhar C, Reddy YSR and De B: Free radicals, antioxidants, diseases and phytomedicines: Current status and future prospect, International J of Pharma Sciences Review and Research 2010; 3: 91-100.
- Kamboj VP: Herbal medicine. Current Science 2000; 78: 35-39.
- Verma S and Singh SP: Current and future status of herbal medicines: Veterinary World 2006; 1: 347-350.
- Mian-Ying W, Brett JW, Jensen CJ, Nowicki D, Chen S, Palu AK and Anderson G: Morinda citrifolia (NoniA literature review and recent advances in Noni research. Acta Pharmacological Sinica 2002; 23: 1127-1141.
- Craig CR and Stitzel RE: Modern Pharmacology with Clinical Applications. Lippincott Williams & Wilkins, Philadelphia 5th 2003; (7): 89-832.
- Osterweis M, Kleinman A and Mechanic D: Editors Institute of Medicine (US) Committee on Pain, Disability, and Chronic Illness Behavior; Pain and Disability: Clinical, Behavioral, and Public Policy Perspectives. Washington (DC): National Academies Press (US); The Anatomy and Physiology of Pain 1987; 7(1): 77-90.
- Dubin AE and Patapoutian A: Nociceptors: the sensors of the pain pathway. J Clin Invest 2010; 120(11): 3760–3772.
- Neil MJ: Clonidine: clinical pharmacology and therapeutic use in pain management. Curr Clin Pharmacol 2011; 6(4): 280–287.
- Bannister K: What do monoamines do in pain modulation. Curr Opin Support Palliat Care 2016; 10(2): 143–148.
- Cisewski DH and Motov SM: Essential pharmacologic options for acute pain management in the emergency setting. Turk J Emerg Med 2018; 19(1): 1–11.
- Kaye AD, Baluch A, Kaye AJ, Gebhard R, Ralf G and Lubarsky D: Pharmacology of cyclooxygenase-2 inhibitors and preemptive analgesia in acute pain management. Curr Opin Anaesthesiol 2008; 21(4): 439–445.
- Li L, Ma P, Cao Y, Tao L and Tao Y: Single-dose and multiple-dose pharmacokinetics of zaltoprofen after oral administration in healthy Chinese volunteers. J Biomed Res 2011; 25(1): 56-62.
- Nagore DH, Ghosh VK, Patil MJ and Wahile AM: In Vitro Antioxidant and In-vivo anti-inflammatory Activity of Cassia sophera Linn, International Journal of Pharmacy And Pharmaceutical Sciences 2010; 2(1): 114-121.
- Harisha CR, Ashok BK, Acharya R, Sukla VJ and Ravishankar B: Anti Inflammatory and Analgesic Activity of Roots and Stem of Cissus repeda Pharmacognosy Journal 2010; 21(18): 7-54.
- Vittalrao AM, Shanbhag T, Kumari KM, Bairy KL and Shenoy S: Evaluation of antiinflammatory and analgesic activitiesof alcoholic extract of Kaempferia galanga in rats. Indian J Physiol Pharmacol 2011; 55(1): 13–24.
- Bukhari IA, Khan RA, Gilani AU, Shah AJ, Hussain J and Ahmad VU: The analgesic, anti-inflammatory and calcium antagonist potential of Tanacetum artemisioides. Arch Pharm Res 2007; 30(3): 303-312.
- Joseph JM, Sowndhararajan K and Manian S: Evaluation of Analgesic and Anti-inflammatory Potential of Heydyotis parberula( G.Don)R.Br.ex.Arn. in experimental animal models. Food Chem Toxicol 2010; 48(7): 1876-1880.
- Silva J, Abebe W, Sousa SM, Duarte VG, Machadoand MIL and Matos MJA: Analgesic and anti-inflammatory effects of essential oils of Eucalyptus, Journal of Ethnopharmacology 2003; 89(2-3): 277-283.
- Bettina M. Ruppett, Edna F. R. Peveria and Lilia C: Gonccalves and Nuno A. Pereira. Pharmacological screening of plants recommended by Folk medicine as anti-snake venom-1, analgesic and Anti-inflammtory activities, Mem. Inst. Oswaldo Cruz Rio de Janeiro 1991; 86(2): 203-205.
- Malairajan P, Gopalakrishnan G, Narasimhan S and Veni JK: Analgesic activity of some Indian medicinal plants Journal of Ethnopharmacology 2006; 106(3): 425-428.
- Husni Twaij and Hantash Abed El-Jalil: Evaluation of Narcotic (Opioid Like) Analgesic Activities of Medicinal Plants, European J of Scientific Res 2009; 33(1): 179- 182.
- Mittal V, Sharma SK, Kaushik D, Khatri M and Tomar K: A comparative study of analgesic activity of Plumbago zeylanica callus and root extracts in experimentalmice, Research Journal of Pharmaceutical, Biological and Chemical Sciences 2010); 1(4): 830.
- Amresh G, Zeashan H, Rao VC and Singh PN: Prostaglandin mediated anti-inflammatory and analgesic activity of Cissampelos pareira, Acta Pharmaceutica Sciencia 2007; 49: 153-160.
- Vijayamirtharaj R, Vincent S and Senthilkumar N: Analgesic activity of Clerodendrum phlomidis (Aerial parts), International J of Research in Pharma and Biomedical Sciences 2011; 2(1): 120-123.
- Yadav S, Kulshreshtha M, Goswami M, Rao CV and Sharma V: Elucidation of Analgesic and Antipyretic activities of Ficus bengalensis linn. Leaves in rats, Journal of Applied Pharmaceutical Science 2011; 01(01): 38-41.
- Isnatin M, Ferdiyanto D and Sufi D: Analgesic activity of ethanolic extract of Manihot esculenta Crantz leaves in mice, Universa Medicina 2011; 1(1): 3-10.
- Hanson GR, Venturelli PJ and Fleckenstein AE: Drugs and society, Boston, Mass: Jones and Bartlett Edi 2011; 10.
- Fan SH, Noraisah AA and Dayang FB: Evaluation of analgesic activity of the methanol extract from the galls of Quercus infectoria (Olivier) in rats. J Evid Based Complementary Altern Med 2014; 10(11): 1–6.
- Rates SMK: Plants as source of drugs. Toxicon 2001; 29: 603–13.
- Zainul AZ, Hijaz MS, Manraj SC, Arifah AK, Teh LK and Mohd ZS: Antinociceptive activity of methanolic extract of Muntingia calabura leaves: further elucidation of the possible mechanisms. BMC Complement Altern Medicin 2014; 14: 63–75.
- Asie S, Majid M, Sima N and Manijeh M: Evaluation of anti-inflammatory and analgesic activity of the extract and fractions of Astragalus hamosus in animal models. Iran J Pharm Res 2015; 1(4): 263–9.
- Roberts MF and Wink M: Introduction. In: Roberts MF, Wink M, editors. Alkaloids: biochemistry, ecology, and medicinal applications. Springer Street, New York: Plenum Press 1998; 1-7.
- Amir MK, Rizwana AQ, Faizan U, Syed AG, Asia N, Sumaira S, Muhammad KL, Muhammad YL, Shafiq UR, Ishtiaq H and Waheed M: Phytochemical analysis of selected medicinal plants of Margalla hills and surroundings. J Med Plants Res 2011; 5: 6017–23.
- Yogesh B, YV and Sumitra C: Brine shrimp cytotoxicity, anti-inflammatory and analgesic properties of Woodfordia fruticosa Kurz flowers. Iran J Pharm Res 2012; 11: 851-61.
- Wahid AM, Suyog DM, Suraj BJ, Ajinkya MP, Mukhtar SK and Madhukar RV: Evaluation of antiinflammatory and analgesic activities of ethanolic extract of roots Adhatoda vasica Linn. International Journal of PharmTech Research 2010; 2: 1364–8.
- Ibironke GF and Ajiboye KI: Studies on the anti-inflammatory and analgesic properties of ambrosioides leaf extract in rats. Int J Pharm 2007; 3: 111–5.
- Zhenga CJ, Tangb WZ, Huanga BK, Hana T, Zhanga QY, Zhanga H and Qin LP: Bioactivity-guided fractionation for analgesic properties and constituents of Vitex negundo L. seeds. Phytomedicine 2009; 16: 560–7.
- Loubna F, Amine L, Rachida A, Ahmed B and Abderrahman C: Evaluation of the analgesic effect of alkaloid extract of Peganum harmala Possible mechanisms involved. J Ethnopharm 2008; 115: 449–54.
- Lin LW, Chen HY, Wu CR, Liao PM, Lin YT, Hsieh MT and Ching H: Comparison with various parts of Broussonetia papyrifera as to the antinociceptive and anti-inflammatory activities in rodents. Biosci Biotechnol Biochem 2008; 72: 2377–84.
- Alfieri A, Maione F, Bisio A, Romussi G, Mascolo N and Cicala C: Effect of a diterpenoid from Salvia cinnabarina on arterial blood pressure in rats. Phytother Res 2007; 7: 690–2.
- Maione F, Cicala C, Musciacco G, De Feo V, Amat AG, Ialenti A and Mascolo N: Phenols, alkaloids and terpenes from medicinal plants with antihypertensive and vasorelaxant activities: a review of natural products as leads to potential therapeutic agents. Nat Prod Commun 2013; 4: 539–44.
- Paulino N, Dantas AP, Bankova V, Longhi DT, Scremin A and Decastro SL: Bulgarian propolis induces analgesics and antiinflammatory effects in mice and inhibits in-vitro contraction of airway smooth muscle. J Pharmacol Sci 2003; 93: 307–13.
- Malmberg AB and Yaksh TL: Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharm Exp Ther 1992; 263: 136–46.
- Verma PR, Joharapurkar AA, Chatpalliwar VA and Asnani AJ: Antinociceptive activity of alcoholic extract of Hemidesmus indicus R.Br. in mice. J Ethnopharmacol 2005; 102: 298–301.
How to cite this article:
Asthana A and Sharma N: Review article: analgesic activity of a potential source of modern medicine. Int J Pharm Sci & Res 2023; 14(1): 109-13. doi: 10.13040/IJPSR.0975-8232.14(1).109-13.
All © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
12
109-113
510 KB
392
English
IJPSR
Amrita Asthana and Neeraj Sharma
Department of Pharmacy, Bhagwant University, Rajasthan Sikar Rode, Ajmer, Rajasthan, India.
amritaasthanaamh@gmail.com
09 May 2022
15 June 2022
30 June 2022
10.13040/IJPSR.0975-8232.14(1).109-13
01 January 2023