ANALGESIC AND ANTI-INFLAMMATORY HERBS: A POTENTIAL SOURCE OF MODERN MEDICINE

ANALGESIC AND ANTI-INFLAMMATORY HERBS: A POTENTIAL SOURCE OF MODERN MEDICINE

Saikat Sen*, Raja Chakraborty , Biplab De , T. Ganesh, H. G. Raghavendra  and Subal Debnath

Creative Educational Society’s College of Pharmacy , Kurnool, Andhra Pradesh, India

Regional Institute of Pharmaceutical Science and Technology , Agartala, Tripura, India

Srikrupa Institute of Pharmaceutical Sciences , Siddipet, Andhra Pradesh, India

ABSTRACT

In recent time, scientific investigations of medicinal plants using indigenous medical systems has attracted a lot of attention globally. Nature has bestowed our planet with an enormous wealth of medicinal plants have been known for millennia and are highly esteemed all over the world as a rich source of therapeutic agents for the prevention and cure of diseases and ailments. Inflammation is complex biological response of vascular tissue due to different harmful stimuli and pain is discomfort signals result of actual or potential injury to the body may associate with inflammation. Inflammation with pain is associated with different diseases like rheumatism, encephalitis, pneumonia, oesophagitis, cancer, heart problems, fibrosis etc.  Nonsteroidal anti-inflammatory drugs and opioid analgesic are normally used in the treatment of inflammation and pain but can cause a lot of adverse effect. Therefore herbal drugs can be potential source to replace them. Every year a lot of plants form traditional medicinal system has been screened for their potential anti-inflammatory and analgesic activity but only few of them only included in health care system after clinical research. So this is time to give more emphasis on research work based on natural sources, investigate the active phytoconstituents, use them on specific treatment, find out adverse effect and to work towards tapping their therapeutic utility.

INTRODUCTION: Plants are important and basic of preventive and curative health cares system since immemorial. Disease is as old as mankind and use of indigenous herbal medicine is a very ancient art and an integral part of treatment ¹. Traditional medicinal herbs have served as a potential source of alternative medicine and different healthcare products. Knowledge of herbal medicines has derived from rich traditions of ancient civilizations and scientific heritage. From ancient 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, nearly 75-80% of world population still depends on herbal medicines. Active constituents from plant sources directly used as therapeutic agent and phytoconstituents are also served as lead molecule for the synthesis of various drugs ^{2, 3}. Folk medicine and their use against diseases in different cultures is a vast traditional knowledge; which is based on the necessities, instinct, observation, trial and error and long experience of ancient/tribal people ⁴. Indigenous or herbal medicines confer considerable economic benefits to most rural and poor people. WHO noted that about 25% of modern medicines are descended from plants sources used traditionally and research on traditional medicinal herbal plant leads discovery of 75% of herbal drugs ³.

Over last decades, there has been extensive interest in the use of herbal medicines therefore the research work and screening of plant has been increased gradually. Different inflammatory diseases are major cause of morbidity and mortality ⁵. Recent years documented progressive increase in the screening and research of medicinal plant with anti-inflammatory and analgesic activity but only few of them only included in health care system after clinical research ⁶. So this is the time for systemic study of plant, isolate the active phytoconstituents, investigate their therapeutic, toxic dose and work towards tapping their therapeutic utility. Therefore this review documented 42 plants from 27 different families which proved useful as analgesic and anti-inflammatory agent; and can be a potential source of medicine in our healthcare system.

Inflammation: Inflammation is a complex response in the vascularized connective tissue occurs due to exogenous and endogenous stimuli. Inflammation is a normal, protective response to tissue injury caused by physical trauma, noxious chemicals or microbiologic agents, which is a part of the host defense. It endeavor to inactivate or destroy foreign organisms, eliminate irritants which is the first phase of tissue repair. Inflammatory process usually subside on completion of healing process but sometimes inflammation turns to severe, which may be far worse than the disease and in extreme cases, it may be fatal also ^{7, 8, 9}. Inflammatory process is characterized by reoccurrence of several phenomenons like initiation, chemoattraction of inflammatory cells and activation of these cells to release inflammatory mediators.

Redness, increased temperature, swelling, pain, and loss of function are the classical sign of inflammation ¹⁰.Inflammation can be provoked by a wide variety of noxious agents, foreign materials, toxins, infections, frostbite, chemicals, pathogens, antibodies, necrosis, blunt, immune reaction and physical injuries ¹¹. Different inflammatory mediators such as histamine, serotonin, kinins (bradykinin), neuropeptides, eicosanoids (prostaglandins  and leukotriene B4, C4, D4, E4), nitric oxide, biological oxidants, platelet activating factors, tumor narcosis factor, oxygen metabolites, complement proteins, cytokines, adhesion factors, and digestive enzymes are plays important role in pathogenesis of inflammation ^{12, 13}. Different cells like neutrophils, eosinophils, monocytes, lymphocytes, basophils, mast cells, connective tissue fibroblasts, resident macrophages and lymphocytes are also involved in pathogenesis of inflammation ¹⁴.

Types of Inflammation: Inflammation is generally divided into two types i) acute inflammation and ii) chronic inflammation. Inflammatory reactions arbitrate by different mechanisms and occur in phases like ¹³;

• Acute phase - temporary local vasodilation and increased capillary permeability
• Delayed, sub-acute phase - infiltration of leukocytes and phagocytic cells
• Chronic proliferative phase - tissue deterioration and fibrosis

Acute inflammation is initial response of the body to risk factors like an infection or trauma etc., this is non-specific and first line of defense of the body against danger ¹⁵. Main features of acute inflammation include a) accumulation of fluid and plasma at the affected site, b) intravascular activation of platelets, c) polymorpho-nuclear neutrophils as inflammatory cells ¹⁶. When the risk factors lengthen and are not removed, acute inflammation will then turns and extend to chronic inflammation. It occurs for a longer duration and associated with the presence of macrophages, lymphocytes, blood cell proliferation, fibrosis and tissue necrosis. The macrophages produce a wide number of biologically active products which leads to tissue destruction and fibrosis characteristics of chronic inflammation ^{17, 18}.

Inflammatory Diseases: Abnormalities related with inflammation comprise a large, officially distinct group of disorders which trigger a vast variety of human diseases. The immune system is often involved with inflammatory disorders. Autoimmune disease, allergic reactions and some myopathies are common type of inflammatory disease. Cancer, atherosclerosis and ischaemic heart disease are some common non-immune diseases with etiological origins in inflammatory processes ⁶. Table 1 listed some of the acute and chronic inflammatory disorder.

TABLE 1: SOME OF THE COMMON TYPES OF INFLAMMATORY DISEASE ^{8, 12, 19, 20}

Pain: Pain is a subjective, multidimensional and unpleasant experience allied with actual or potential tissue damage comprising sensory (e.g., intensity, duration, location), affective (e.g., unpleasantness, emotional, motivational), and cognitive (e.g., awareness of the implications, fear, anxiety) components ²¹. Pain has both sensory (somatic) and psychological (affective) mechanism. However, pain is more than a sensation or the physical alertness; it also includes perception, the subjective interpretation of the discomfort ^{10, 21}.

The pain reaction is transmitted over the reflex arc by sensory fibers in the dorsal horn of the spinal cord and by synapsing motor neurons in the anterior horn. Due to harmful stimulus anatomic pattern of sensory and motor neurons move quickly, nerve impulses alerting the individual to move away from such stimuli are simultaneously sent along efferent nerve fibers from the brain ¹⁰. Bradykinin, histamine, prostaglandins are major mediators of pain. Different types of pain include ^{10, 22, 24, 25}:

1. Somatic pain: caused by the activation of pain receptors in either the body surface or musculoskeletal tissues, which may be caused by a combination of factors likes abnormalities, inflammation, repetitive trauma, excessive activity, vigorous stretching and contractions due to paralysis.
2. Visceral pain: associated with the damage of internal organs and is most common form of pain, this is result by the activation of pain receptors in the chest, abdomen or pelvic areas.
3. Neuropathic pain: caused by injury or malfunction to the spinal cord and peripheral nerves associated with burning, tingling, shooting, stinging, pins and needles sensation.
4. Acute pain: results from tissue damage or injury, but usually goes away as the injury heals or the cause of the pain is removed. It is short lasting and usually manifests in ways that can be easily described and observed.
5. Chronic pain: pain lasting for more than three months and more subjective, treating chronic pain possess a great challenge for physicians as it has ability to change the function and quality of life.

Synthetic Analgesic and Anti-Inflammatory Drugs: Non steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce inflammation, pain and fever. NSAIDs inhibit cyclo-oxygenase (COX) enzyme results inhibition of prostaglandin synthesis. NSAIDs are usually consider as mild analgesics and particularly effective when inflammation has results sensitization of pain receptors to normally painless mechanical or chemical stimuli ¹².

However, for severe or chronic malignant pain, opioids analgesics are the drugs of choice⁸. The greatest drawback in the available potent synthetic analgesic and anti-inflammatory drugs lies in their adverse effect, toxicity and reappearance of symptoms after discontinuation. Table 2 tabulated adverse or toxic effect of some of the commonly available modern drugs used for treatment of pain and inflammation.

TABLE 2: SOME OF THE COMMONLY USED ANALGESIC AND ANTI-INFLAMMATORY DRUGS AND THEIR ADVERSE EFFECT ^{8, 10, 20}:

Herbal Anti-inflammatory Agents: Herbal medicines are the synthesis of remedial experiences and practice of indigenous systems of medicine for over hundreds of years. Despite the tremendous progress in medical research during the past decades, the treatment of many serious diseases including pain and inflammation is still problematic ²⁶. Currently used anti-inflammatory and analgesic drugs are associated with some severe side effects; therefore there is a need for the development of potent analgesic and anti-inflammatory drugs with fewer side effects ²⁷. Herbal medicine showed safety, efficacy, cultural acceptability and lesser side effects than the synthetic drugs. The number of chemical compounds, found within the plant kingdom is a part of the physiological functions of living flora and are supposed to have better compatibility with the human body ². Different phytoconstituents like alkaloids, flavonoids, xanthone, coumarin, sterols, withaferin-A, andrographolide etc., are also proved effective as analgesic and anti-inflammatory agent ^{5, 6}. Therefore it is the demand of time to investigate and herbal medicine and uses them in our daily life. Table 3 tabulated some of the plant reported to demonstrate pain and inflammation reducing properties.

TABLE 3: SOME OF PLANT SOURCE WITH ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY ^26-64:

CONCLUSION: Plants have been medicine and food for animals, since animal life emerged. Plants contain a large number of spread of pharmacologically active ingredients and each herb has its own unique combination and properties. A number of plants have been described in Ayurveda and other traditional medicinal system for the management of different diseases according to the perceived needs of the patient and based upon the individual herb’s constituents. Diseases with pain and inflammation are a widespread and required more attention. Review of herbal medicine used by different medicinal system and tribal/ethnic people in pain and inflammation is essentially quite important in the face of treatment. A large number of people these days are looking for herbal remedies and relief for their ailments. The cause for this is the quest for a natural and safe way to treat disease. Therefore, our efforts should be directed towards the review of medicinal plant, screening of activity, isolation and characterization of the active principles and elucidation of the relationship between structure and activity, that can aimed at towards clinical relevance.

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