Medicinal Properties of Terminalia Arjuna: A Review

Terminalia arjuna, also commonly referred to as T. arjuna, is a deciduous tree that belongs to the family Combretaceae. It can be found in many regions of India. T. arjuna is a 60to 80-foot-tall tree found alongside rivers and streams all over the Indo-sub-Himalayan areas of Delhi, Uttar Pradesh, Chota Nagpur, the southern part of Bihar, Madhya Pradesh and Deccan regions. It has been used to cure several ailments for as far back as the ancient times of India. It is most prevalently consumed to cure and manage several cardiac and vascular diseases, including those like CADs, Angina Pectoris, CHF/Hypertension, and Dyslipidaemia. Its extracts are used to improve cardiac muscles and thus effectively improve heart pumping, heart rate, and blood pressure. The many parts of the tree consist of several phytochemicals, including tannins, flavonoids, glycosides, and triterpenoids like Arjunolic acid, which contribute to its anti-oxidant anti-inflammatory antimicrobial, anticarcinogenic and antimutagenic properties. As of today, there have not been any reports of any harmful side effects regarding its administration. While there are various studies that support its use for a problem of diseases, further research is still required to understand its exact mechanisms. There is also a need for further research on T. arjuna regarding its drug interactions, its specific molecular mechanism of action, and the toxicology involved. Review Article Verma and Jogdand; JPRI, 33(62A): 593-604, 2021; Article no.JPRI80456 594


INTRODUCTION
Plants with therapeutic characteristics have long been utilized to heal ailments for thousands of years. [1]. WHO statistics estimate that approximately 80% of the world's population, including 60% of India's rural population, depend on these therapeutic agents [2]. The demand for herbal medicines has only increased in recent years. Due to their easy accessibility, efficiency, and rare side effects. These medicinal plants contain certain bioactive substances such as alkaloids, tannins, carbohydrates, steroids, terpenoids, phenols, and flavonoids, ensuring certain physiological effects on the body [3].
A variety of medicinal plants have been employed in modern-day healthcare, including: There are a variety of medicinal plants in India which have been extensively employed in Ayurvedic practices. T. arjuna is one of these plants, and it has proven to be one of the most commonly acknowledged herbal medicines for the treatment of a range of disorders [1].

T. arjuna: Overview
T. arjuna of the family Combretaceae. Long used as a cardioprotective agent, it was first introduced by Vagabhatta, who advocated its stem bark powder's use for heart diseases and has since been written in various ancient texts like the Sushruta Samhita, Charaka Samhita, and Ashtang Hridayam. [5].
T. arjuna is a 60-to 80-foot-tall tree found alongside rivers and streams all over the Indosub-Himalayan areas of Delhi, Uttar Pradesh, Chota Nagpur, the southern part of Bihar, Madhya Pradesh, and Deccan regions. Aside from being found in various regions of India, it has also been seen in many other countries, including Sri Lanka, Burma as well as Mauritius [6,7]. Although this plant grows on all types of soil, it has shown a preference for red lateric, fertile loam and humid soil.
The tree's bark has a smooth outer surface and an inner striated pinkish surface [8]. During April and May, the bark of this tree sheds away [9].

Chemical Components of Terminalia arjuna
The learoots roots, fruits, ste, as well as ieeds of T.arjuna, have been used in medical practice due to their different phytoconstituents.

TERPENOIDS, URSANE TRITERPENO-IDS AND GLYCOSIDES
Triterpenoids are structurally diverse organic compounds which include various varieties, due to modifications in its basic backbone, including ursolic and oleanolic acid [39].
The   Luteolin, a molecule isolated from the butanolic fraction, exhibits antimutagenic properties [1]. It also has a very efficient antibacterial property as it inhibits gram negative pathogenic growth with the minimum inhibitory concentration of 12.5μg/disc.
The phenolic content contributes to a free radical scavenging action which makes T. arjuna a strong agent against proliferation and oxidation [1,44].
Tannins: Tannins are polyphenols that are water soluble and may be found in a range of plant components. Tannins possess a variety of properties. One such property is that it is an anticarcinogen along with tea polyphenols. It also has an anti-mutagenic property as well as an anti-oxidant property. There three properties are interrelated as oxygen-free radicals are produced by a variety of carcinogens and mutagens. which these tannins ultimately decrease for protecting cellular oxidative cellular damage.
Another important property of tannins is its antimicrobial activity. Studies have shown that Yeasts, fungi, bacteria, and viruses have all been found to be inhibited by tannins.
Tannins also aid in the clotting of blood, the reduction of blood pressure, the reduction of serum cholesterol levels, the production of liver necrosis, and the modulation of immune responses [45].

PHARMACOLOGICAL ACTIVITIES OF Terminalia arjuna
Even though each part of T. arjuna has its own pharmacological effects on the body due to their varying composition, the bark of the tree is regarded to the most clinically relevant.
The bark has been shown to have astringent, expectorant, demulcent, cardiotonic, antidysenteric, styptic and urinary astringent effects, as well as being beneficial in the management of cirrhosis, anaemia, leukorrhea, fractures, cardiomyopathy, diabetes and ulcers [8,46].
Chakradatta introduced an ulcer wash made from an infusion of the bark prepared using milk and perhaps even ghee/butter in Ancient India. The ashes of the bark was employed for the management of snakebites and scorpion stings [47].
It has been used in many forms throughout India for a variety of conditions. T. arjuna's bark is boiled in water and breathed in which then alleviates headaches and eliminate worms in the teeth in the Kancheepuram District of Kerala. They also use its fruit's paste as a topical agent on wounds [48]. The bark powder is mixed with rice water by tribals in the Sundargarh District of Odisha to treat haematuria (there is blood in the urine [49].
A more detailed analysis of the same on the basis of clinical trials and experiments has been tabulated below. Aneja et al. [57] The aqueous extract resulted in being an efficient antimicrobial against S. aureus bacteria [58] However, the acetone extract of the leaf extract of T. arjuna was seen to have the most potent antimicrobial agent against S. aureus [1].
The organic extracts were shown to be highly efficient against the proliferation of gram-negative bacteria, with the exception of P. aeruginosa. Cardio-protective potential Terminalia arjuna bark powder which was used for 12 weeks before ischemicreperfusion injury [1] Gauthaman et al [59].
Myocardial endogenous antioxidants were boosted following chronic oral treatment of T. arjuna bark in rabbits. It also induces HSP-72 (Inducible Heat Shock Protein 72). The prevents myocardial ischemic reperfusion injuries due to protection against oxidative stress.

Terminalia arjuna's ethanolic and aqueous extracts
Oberoi et al. [60] T. arjuna's aqueous extracts enhances sarcoplasmic reticular function and thus induces cardiotonic action. Arrhythmias are less likely to arise as a result of this. As a result, T. arjuna's aqueous extract is seems as a safe cardiotonic that is good to heart health and may be used in conjunction with chronic health-care treatment programmes [ T. arjuna bark's ethanolic extract (together with its components) protect against hydrogen peroxide-induced DNA damage [62] The ethyl acetate fraction has especially been effective in maximally inhibiting DPPH, ABTS, metal chelation, hydroxyl and nitric oxide radicals. T. arjuna extracts have also been demonstrated to ameliorate a variety of impairments related to free radical production and DNA damage.

Observation in the concerned clinical trial/experiment
Gastro-productive effect

Methanolic extract of Terminalia arjuna
Devi et al. [63] Two groups of ulcer-induced animals were studied. One group received Diclofenac Sodium (DIC) and T. arjuna, whereas the other received simply Diclofenac Sodium. In comparison to merely providing DIC, the DIC + T. arjuna treatment plan demonstrated a considerable reduction in the lesion index [64] T. arjuna's gastroprotective effect was validated by other histological research.

CARDIOVASCULAR ROLE OF T. arjuna
The bark stem of T. arjuna has inotropic, chronotopic and diuretic properties [7]. Experiments on animals revealed an augmentation in coronary blood flow, which increased the force of cardiac muscle contraction, resulting in a drop in blood pressure along with heart rate as well as bradycardia with accordance with the dose administered [65.66,67,7].
Research done on rats found that pretreatment with atropine reduced the hypotensive effect of T. arjuna with a fraction containing tannin-related chemicals isolated from the aqueous extract. Pretreatment of the rats with propranolol had no impact, suggesting that the hypotensive effect was related to cholinergic processes [31].
In myocardial infarction which is induced by isoprenaline, T. arjuna exhibited PGE2 like activity in the heart by producing vasodilatation and hypotension [5]. T. arjuna's bark extract reduced the oxidative stress which upsurged on induction by isoprenaline and reduced the amount of natural antioxidants in the body [5].
One of the triterpenoids found in T. arjuna, Arjunolic acid, prevents the decline of superoxide dismutase, glutathione peroxidase, catalase, alpha-tocopherol, ceruloplasmin, ascorbic acid, reduced glutathione (GSH), MPO (myeloperoxidase) and lipid peroxide levels, implying that Arjunolic acid's cardioprotection by Arjunolic acid is most likely due to protection against damage to heart via myocardial necrosis [68]. Another study found that arjunolic acid had cardioprotective properties through boosting the body's natural antioxidant defences [69].
When compared to the other fractions of T. arjuna bark, the ethanolic fraction has powerful antioxidant and hypolipidemic effects [74,75]. The down regulation of lipogenic enzymes, the enhances hepatic clearance of cholesterol and inhibition of HMG-CoA reductase are likely to be responsible for the hypolipidemic effect [76].

Angina Pectoris:
A study was undertaken where the sample size of 30 patients suffering from stable angina were administered with 500 mg of T. arjuna bark extract three times a day. The bark's anti-ischemic activity was proven by a considerable reduction in the serum cholesterol levels, systolic blood pressure, plasma cortisol and the mean anginal frequency. There was also an improvement in the ECG changes [5,77].
Chf/ Hypertension: A study was undertaken where the sample size of 10 patients suffering from Congestive Heart Failure (CHF) were given 4g of T. arjuna bark powder twice a day for a month as part of a research. With considerable diuresis, there was enhancement seen with dyspnea, functional class, and general wellbeing. Both the systolic as well as the diastolic blood pressures dropped significantly [78].

TOXICITY AND SIDE EFFECTS OF Terminalia arjuna
Most traditional and herbal medicines like T. arjuna are known for producing the least amount of side effects, hence their popularity. No cases of T. arjuna toxicity have been documented [19].
T. arjuna is most widely used for the cure and control of coronary artery disorders (CAD), with an ideal dose of 1-2 g per day, and 500 mg of the bark extract three times per day for congestive heart failure. The side effects reported in this treatment are rather minor like headaches, mild gastritis and constipation. After more than 2 years of this drug administration, there were no signs of haematological, hepatic, metabolic and renal toxicity [77,79].
A study reported that there was a reduction in thyroid hormone concentration in euthyroid animals and an increase in hepatic LPO (Lipid Peroxidation) upon the administration of T. arjuna. Therefore, care must be taken when consuming this plant extract as it carrier a risk of development of hypothyroidism and hepatotoxicity [80][81][82][83][84][85].

CONCLUSION
T. arjuna, a tree seen all around India, is being utilised for hundreds of years for curing a conundrum of ailments, but more importantly for cardiac health. Its active constituents include tannins, triterpenoids, flavonoids and certain minerals like calcium, magnesium, zinc and copper.
Its extracts are used for the improvement of cardiac muscles, effectively improving heart pumping, heart rate and blood pressure.
Terminalia arjuna can be administered in a variety of conditions such as Angina Pectoris, Congestive Heart Failure, Cardiomyopathy or Post Myocardial Infarction and Hyperlipidemia.
While there are various studies which support their application in clinical practice, such studies lack the standardisation of extract to be used, well conducted studies for long term effects and the bioavailability of the drug.
There is also a need for further research on T. arjuna regarding its drug interactions, its specific molecular mechanism of action as well as toxicology.

NOTE
The study highlights the efficacy of "herbal, ayurvedic,traditional" which is an ancient tradition, used in some parts of India. This ancient concept should be carefully evaluated in the light of modern medical science and can be utilized partially if found suitable.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.