INTRODUCTION:

Herbal medicine has been a part of human culture since the beginning of time. Throughout history, people have relied on herbs and botanicals for their medicinal properties. Even today, many individuals use herbal remedies as a way to maintain their health and treat various ailments. The use of herbs in medicine dates back to ancient civilizations such as Egypt, China, and Greece¹. These civilizations documented the use of plants for medicinal purposes, and many of their practices have been passed down through the generations. Herbal medicine is the use of plants or plant extracts to treat various health conditions. Herbs can be used in a variety of forms, including teas, tinctures, capsules, and topical preparations¹.

One of the benefits of herbal medicine is that it can be used to treat a wide range of conditions. Despite the benefits of herbal medicine, it is important to note that not all herbal remedies are safe or effective. Some herbs can interact with medications or cause side effects². For this reason, it is important to consult with a healthcare provider before using any herbal remedy. In addition, the quality of herbal remedies can vary widely. Some products may be contaminated with harmful substances or may not contain the advertised ingredients³. It is important to purchase herbal remedies from reputable sources and to look for products that have been independently tested for quality and purity. Another challenge with herbal medicine is the lack of standardization in dosing and preparation. Unlike pharmaceutical drugs, which are carefully measured and regulated, herbal remedies can vary widely in their potency and effectiveness. This can make it difficult to determine the optimal dose for a particular herb or to compare the effectiveness of different products⁴. Despite these challenges, herbal medicine remains a valuable tool for promoting health and treating various health conditions. As more research is conducted on the efficacy and safety of herbal remedies, it is likely that more individuals will turn to these natural remedies as a way to maintain their health and well-being⁵.

Analgesics from herbal origin:

Analgesic herbal plants have been used for centuries to relieve pain and discomfort. These plants contain various active compounds known as phytoconstituents, which have analgesic properties^6–8. These compounds work by blocking the transmission of pain signals to the brain, reducing inflammation, and providing a sedative effect ^9,10. One of the most well-known analgesic herbal plants is the opium poppy (Papaver somniferum), which contains a group of compounds called alkaloids, including morphine, codeine, and thebaine. These alkaloids are potent painkillers that work by binding to specific receptors in the brain and spinal cord, which blocks the transmission of pain signals. Morphine is the most active alkaloid and is widely used in modern medicine to relieve severe pain¹¹. Another commonly used analgesic herb is the willow bark (Salix spp.), which contains salicin, a compound that is metabolized into salicylic acid in the body. Salicylic acid is the active ingredient in aspirin, which is widely used to relieve pain and reduce inflammation. Willow bark has been used for centuries to relieve pain and fever, and it is believed to work by inhibiting the production of prostaglandins, which are involved in the inflammatory response. Turmeric (Curcuma longa) is another analgesic herb that has been used for centuries in traditional Indian medicine. Turmeric contains a group of compounds known as curcuminoids, which have anti-inflammatory and analgesic properties. Curcumin is the most active curcuminoid and is believed to work by inhibiting the production of inflammatory cytokines and blocking the transmission of pain signals¹².

Alkaloids:

Alkaloids are a class of compounds found in various plants that have diverse biological activities, including analgesic properties. Alkaloids exert their analgesic effects by interacting with opioid receptors in the central and peripheral nervous systems. In the central nervous system, alkaloids such as morphine and codeine bind to the mu opioid receptor, which is involved in pain regulation, to produce their analgesic effects. The activation of mu opioid receptors leads to a decrease in the release of neurotransmitters such as substance P and glutamate, which are involved in the transmission of pain signals. In addition to their central effects, alkaloids also have peripheral analgesic effects. Peripheral opioid receptors are located in various tissues, including the skin, muscles, and joints. When activated, these receptors inhibit the release of inflammatory mediators such as prostaglandins, which contribute to the development of pain and inflammation. Alkaloids also have anti-inflammatory properties, which contribute to their analgesic effects¹³. One mechanism by which alkaloids exert their anti-inflammatory effects is by inhibiting the activity of the enzyme cyclooxygenase-2 (COX-2), which is involved in the synthesis of prostaglandins. By inhibiting COX-2, alkaloids reduce the production of prostaglandins, which in turn reduces inflammation and pain¹⁴.

Analgesics Effect of Indole Alkaloids:

Indole alkaloids are a class of alkaloids that are widely distributed in nature, and are found in a variety of plants, fungi, and bacteria. They are characterized by the presence of an indole ring, which is a heterocyclic aromatic ring composed of six carbon atoms and one nitrogen atom. Indole alkaloids have a wide range of biological activities, including antimicrobial, anticancer, antiviral, and analgesic properties^[19]. Indole alkaloids are a diverse class of natural products that contain an indole ring as a common structural motif. The chemistry of indole alkaloids is characterized by a wide variety of functional groups, which can modify the activity and pharmacological properties of these compounds. The indole ring is a heterocyclic aromatic ring that contains six carbon atoms and one nitrogen atom. The nitrogen atom in the indole ring can be protonated or deprotonated, depending on the pH of the solutions. This property of the indole ring plays an important role in the biological activity of indole alkaloids¹⁵.

Mitragynine:

Mitragynine is the primary psychoactive indole alkaloid found in the leaves of the Southeast Asian plant Kratom (Mitragyna speciosa). It is known for its analgesic effects and is used traditionally for pain relief. Studies have shown that mitragynine produces analgesic effects in acute pain animal models, and its mechanisms of action are believed to involve interactions with various receptors and neurotransmitters.Mitragynine has been found to interact with the mu, delta, and kappa opioid receptors, which are involved in pain perception and modulation. The mu opioid receptor is responsible for the analgesic effects of opioids, and mitragynine has been found to have a high affinity for this receptor. This interaction leads to the inhibition of pain signals in the spinal cord and brain, resulting in analgesia^[18].In addition to its interaction with opioid receptors, mitragynine has been found to affect other neurotransmitter systems, including the serotonin and dopamine systems. Mitragynine has been found to act as a partial agonist of the 5-HT2A receptor, which is involved in pain perception, mood regulation, and the stress response. This interaction may contribute to the analgesic effects of mitragynine, as well as its anxiolytic and anti-depressant effects ¹⁶.

7-hydroxymitragynine:

Kratom is a plant native to Southeast Asia that has been traditionally used for its medicinal properties, including pain relief. One of the active compounds found in kratom is 7-hydroxymitragynine (7-HMG), which has been identified as a potent analgesic and is believed to be responsible for much of the plant's pain-relieving effects.The molecular mechanism of action of 7-HMG is complex and not fully understood, but it is known to interact with the mu-opioid receptor in the brain, which is the target of many commonly used opioids such as morphine and fentanyl. However, unlike these drugs, 7-HMG does not appear to produce significant respiratory depression or other adverse effects associated with traditional opioids¹⁷.

Kopsinine:

Kopsinine is a monoterpenoid indole alkaloid found in Kopsia officinalis, which has been shown to possess analgesic properties^[29]. Several studies have investigated the molecular mechanisms of action of kopsinine in producing its analgesic effects.One of the proposed mechanisms of action of kopsinine is through its interaction with opioid receptors. In a study, the analgesic effects of kopsinine were evaluated using the hot plate and acetic acid-induced writhing tests in mice. Pretreatment with naloxone, an opioid receptor antagonist, was found to significantly attenuate the analgesic effects of kopsinine, suggesting that its analgesic effects may be mediated, at least in part, through opioid receptors¹⁸.

Gelstriamine A:

Gelstriamine A is a novel Triamino Monoterpene Indole Alkaloid isolated from Gelsemium elegans stems, a traditional Chinese medicinal plant known for its analgesic and sedative properties. The alkaloid possesses a unique caged 6/5/7/6/6/5 scaffold and exhibits significant analgesic activity in mice models of pain ^[34].One study found that Gelstriamine A acts as a potent and selective antagonist of the N-methyl-D-aspartate (NMDA) receptor, a type of glutamate receptor involved in the transmission and modulation of pain signals in the central nervous system. By blocking the activity of NMDA receptors, Gelstriamine A may prevent the amplification of pain signals and reduce the intensity of pain experienced by the individual¹⁵.

CONCLUSION:

The analgesic potential of indole alkaloids presents a promising avenue for further exploration in the field of pain management. Indole alkaloids, derived from various natural sources such as plants and fungi, have exhibited notable analgesic properties in preclinical studies^19–21. Through complex interactions with the central nervous system, especially by altering neurotransmitter pathways implicated in pain perception, these substances exhibit their analgesic effects. Notably, indole alkaloids have shown effectiveness in models of neuropathic and inflammatory pain, indicating a wide range of analgesic action.Additionally, indole alkaloids' varied chemical structures offer a wealth of resources for the creation of new analgesics. To improve their therapeutic potential and get a deeper understanding of their mechanisms of action, researchers are concentrating more on the isolation and synthesis of particular indole alkaloids. Even with the encouraging preclinical data, more thorough clinical research is necessary to confirm the indole alkaloids' analgesic effectiveness, safety, and tolerability in people.

REFERENCES:

1. Al-Snafi AE. Medicinal plants possessed anti-inflammatory antipyretic and analgesic activities (part 2)-plant based review. Sch Acad J Pharm. 2016; 5(5): 142–58. doi:10.2174/1381612820666150115151416

2. Rao TD, Kumar MP. Analgesic efficacy of paracetamol vs ketorolac after dental extractions. Res J Pharm Technol. 2018; 11(8): 3375–9. doi:10.5958/0974-360X.2018.00155.8

3. Suryadi A, Siswodihardjo S, Widiandani T, Widyowati R. Structure modifications of pinostrobin from Temu Kunci (Boesenbergia pandurata Roxb. Schlecht) and their analgesic activity based on in silico studies. Res J Pharm Technol. 2021; 14(4): 2089–94. doi:10.5958/0974-360X.2021.01055.6

4. Gidwani BK, Bhargava S, Rao SP, Majoomdar A, Pawar DP, Alaspure RN. Analgesic, anti–inflammatory and anti–hemorrhoidal activity of aqueous extract of Lantana camara Linn. Res J Pharm Technol. 2009; 2(2): 378–81. doi:10.5958/0974-360X-2009-0032-7

5. Mirzaeian R, Sadoughi F, Tahmasebian S, Mojahedi M. The role of herbal medicines in health care quality and the related challenges. J Herb Med Pharmacol. 2021; 10(2): 156–65. doi:10.4103/jhmp.JHMP_1_21

6. Paswan SK, Srivastava S, Rao CV. Incision wound healing, anti-inflammatory and analgesic activity of Amaranthus spinosus in Wistar rats. Res J Pharm Technol. 2020; 13(5): 2439–44. doi:10.5958/0974-360X.2020.01480.8

7. Ghori SS, Khan M, Qureshi MS, Ghori SK. Analgesic and antipyretic effects of Ficus dalhouseae Miq. leaf ethanolic extract. Res J Pharm Technol. 2014; 7(9): 1014–9. doi:10.5958/0974-360X.2014.00827.4

8. Valli G, Vasanthi A, Vijayalakshmi R, Thirupathi AT. CNS depressant and analgesic activities of different extracts of Tephrosia purpurea root. Res J Pharm Technol. 2011; 4(9): 1439–42. doi:10.5958/0974-360X.2011.00940.2

9. Muthusamy P, Nivedhitha M, Jayshree N. Analgesic and anti-inflammatory activities of Datura metel Linn. root in experimental animal models. Res J Pharm Technol. 2010; 3(3): 897–9. doi:10.5958/0974-360X.2010.00346.8

10. Bachhav RS, Buchake VV, Saudagar RB. Analgesic and anti-inflammatory activities of Anthocephalus cadamba Roxb. leaves in Wistar rats. Res J Pharm Technol. 2009; 2(1): 164–7. doi:10.5958/0974-360X-2009-00044-0

11. Cain CK, Francis JM, Plone MA, Emerich DF, Lindner MD. Pain-related disability and effects of chronic morphine in the adjuvant-induced arthritis model of chronic pain. Physiol Behav. 1997; 62(1): 199–205. doi:10.1016/S0031-9384(96)00215-4

12. Xiao X, Wang X, Gui X, Chen L, Huang B. Natural flavonoids as promising analgesic candidates: A systematic review. Chem Biodivers. 2016; 13: 1427–40. doi:10.1002/cbdv.201600014

13. Singh SS, Pandey SC, Srivastava S, Gupta VS, Patro B, Ghosh AC. Chemistry and medicinal properties of Tinospora cordifolia. Indian J Pharmacol. 2003; 35(2): 83–91. doi:10.4103/0253-7613.36555

14. Kumar GP, Khanum F. Neuroprotective potential of phytochemicals. Pharmacogn Rev. 2012; 6(12): 81–90. doi:10.4103/0973-1296.101103

15. Jin P, Zhan G, Zheng G, Liu J, Peng X, Huang L, et al. Gelstriamine A, a triamino monoterpene indole alkaloid with a caged 6/5/7/6/6/5 scaffold and analgesic alkaloids from Gelsemium elegans stems. J Nat Prod. 2021; 84(4): 1326–34. doi:10.1021/acs.jnatprod.0c01035

16. Mat NH, Bakar SNS, Murugaiyah V, Chawarski MC, Hassan Z. Analgesic effects of main indole alkaloid of kratom, mitragynine, in an acute pain animal model. Behav Brain Res. 2023; 439: 114251. doi:10.1016/j.bbr.2022.114251

17. Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sci. 2004; 74(17): 2143–55. doi:10.1016/j.lfs.2004.04.009

18. Jin Q, Zhao YL, Liu YP, Zhang RS, Zhu PF, Zhao LQ, et al. Anti-inflammatory and analgesic monoterpenoid indole alkaloids of Kopsia officinalis. J Ethnopharmacol. 2022; 285: 114848. doi:10.1016/j.jep.2021.114848

19. Kaur M, Kaur H. Analgesic activity of roots of Aralia racemosa. Res J Pharm Technol. 2011; 4(12): 1896–7. doi:10.5958/0974-360X.2011.01215.4

20. Alsayari A, Ghazwani M, Almaghaslah D, Alhamhoom Y, Louis J, Altohami J, et al. Potential analgesic and diuretic activity of Crataegus oxyacantha Linn. Res J Pharm Technol. 2018; 11(6): 2476–82. doi:10.5958/0974-360X.2018.00170.8

21. Saptarini NM, Deswati DA. Analgesic and antipyretic activities of ethanolic extract of sappan wood (Caesalpinia sappan L.) leaves. Res J Pharm Technol. 2021; 14(10): 5213–6. doi:10.5958/0974-360X.2021.01511.6

Received on 16.01.2025 Revised on 12.05.2025

Accepted on 18.07.2025 Published on 10.02.2026

Available online from February 16, 2026

Research J. Pharmacy and Technology. 2026;19(2):911-914.

DOI: 10.52711/0974-360X.2026.00129

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