A Review Article of Haritaki (Terminalia chebula Retz.)plant medicinal uses and their Activities

Abstract

Haritaki, or Terminalia chebula Retz., is a valued medicinal herb in Siddha, Unani, and Ayurvedic medicine, renowned for its wide-ranging medicinal properties. Known as the "king of medicines," it contains various bioactive phytoconstituents such as phenolic compounds, glycosides, sterols, flavonoids, and tannins, contributing to its diverse pharmacological effects, including anti-inflammatory, antibacterial, antidiabetic, hepatoprotective, cardioprotective, wound-healing, and anticancer properties. Additionally, it exhibits immunomodulatory and adaptogenic qualities, vital for overall health. This review assesses its ethnomedicinal applications, phytochemistry, and pharmacological research, indicating Haritaki potential for modern drug development, though further clinical trials and mechanistic studies are necessary to confirm its efficacy and safety.

Keywords

Introduction

Figure: Haritaki (Terminalia Chebula Retz.)

Etymology (Meaning)

The Sanskrit name “Haritaki” comes from “Harita” meaning green or that which removes diseases (Hariti rogam).

It is called Abhaya meaning “fearless,” as it is believed to remove fear of disease and death in Ayurvedic texts.

Names in Indian Languages

Table: Names in Indian Languages

Geographical sources

India, Sri Lanka, Nepal, Bangladesh, Malaysia, and Vietnam are among the subtropical and tropical regions of Southern and Southeast Asia where Haritaki (Terminalia chebula Retz.) is mainly found. It grows in the southern region of India, the central provinces, the northern woods, and the sub-Himalayan tract.

Morphological / Botanical Description

1. Habit:

• A medium to large deciduous tree, growing up to 25–30 meters in height.
• The trunk is straight, with dark brown to blackish bark, having longitudinal cracks.

2. Leaves:

• Simple, opposite or sub-opposite, ovate to elliptic in shape.
• Size: 7–18 cm long and 4–10 cm broad.
• Apex rounded or acute, base rounded, and margin entire.
• Leaves have two large glands at the top of the petiole.
• Surface is glabrous above and pubescent below.

3. Flowers:

• Small, dull white to yellowish, with a strong unpleasant odor.
• Arranged in terminal or axillary spikes or short panicles.
• Unisexual or bisexual, with 5 petals and 5 sepals.
• Blooming season: April to June.

4. Fruits:

• A drupe, ellipsoidal to ovoid, 2–4.5 cm long, yellowish-brown when ripe.
• Five ridges (angles) are often visible on the surface.
• The fruit pulp is used medicinally (the dried pericarp).
• Fruiting season: November to February.

5. Seeds:

• Contained inside the drupe; hard, brown, and single-seeded.

6. Root:

• Well-developed taproot system with numerous lateral roots.

Habitat and Distribution

• Found in tropical and subtropical forests up to 1500 m altitude.
• Common in India, Nepal, Sri Lanka, Myanmar, Thailand, China, and Malaysia.

Microscopic study

When the fruit rind of Haritaki is examined under a microscope, diagnostic characteristics such as lignified tissues, pegged fibers, sclereids, and many stone cells with thick, pitted walls as well as vascular bundles with spiral, pitted, and reticulate thickenings are revealed. There are also calcium oxalate crystals (both rosette and cluster forms), starch grains, and cells that contain tannin. The correct identification and standardization of Haritaki fruit and its formulations depend on the existence and properties of certain microscopic traits.

Extraction Procedure of Haritaki (Terminalia chebula Retz.)

1. Collection and Identification

• Gather Terminalia chebula ripe dried fruits from reliable suppliers.
• To get rid of dust, grime, and foreign objects, thoroughly clean.
• Dry at room temperature in the shade (avoid direct sunshine to avoid losing active chemicals).

2. Drying and Powdering

• Once the fruits have dried, use a mechanical grinder to ground them into a coarse powder.
• To achieve a consistent particle size, pass the powder through a 40-mesh screen.
• To facilitate extraction, store in an airtight container.

3. Extraction Methods

Various techniques can be applied based on the solvent type and goal:

A. Soxhlet Extraction (Common for Laboratory Use)

Materials Required:

• Haritaki powder – 100 g
• Solvent – Ethanol (95%) or Methanol (polar solvent)
• Soxhlet apparatus

Procedure:

• Fill a thimble with 100 g of powdered Haritaki.
  400–500 mL of solvent should be added to the round-bottom flask.
• For six to eight hours, extract continuously in the Soxhlet extractor.
• Following extraction, use a rotary evaporator or water bath set below 50°C to filter the extract and remove the solvent.
• To obtain a solid or semisolid crude extract, the concentrated extract is dried.
• Keep at 4°C in an airtight container.

B. Maceration Method (Simple Traditional Extraction)

Procedure:

• Put 100 grams of course Haritaki powder in a conical flask.
• 500 milliliters of hydroalcoholic solvent (ethanol: water = 70:30) should be added.
• Shake the mixture occasionally for 72 hours.
• Use Whatman filter paper to filter the extract.
• Use a water bath or lower pressure to concentrate the filtrate.
• The extract should be dried and kept in a desiccator.

C. Aqueous Extraction (Traditional Ayurvedic Approach)

Procedure:

• For one hour, bring 100 grams of Haritaki powder to a boil in 1000 milliliters of purified water.
• After cooling, strain the mixture.
• To produce the aqueous extract, evaporate the filtrate until it is completely dry.
• Keep in an airtight, sterile container.

4. Yield and Storage

• Yield: Usually 10–20% depending on solvent polarity.
• Storage: Keep extract in an airtight amber glass container, stored at 4°C to prevent oxidation or microbial contamination.

5. Phytochemicals Extracted

The extract may contain:

• Tannins (chebulinic acid, chebulagic acid, gallic acid)
• Flavonoids
• Phenolic compounds
• Glycosides
• Saponins

Traditional use of Haritaki

1. Due to its laxative, carminative, astringent, and tonic properties, haritaki fruit is widely utilized in Thai traditional medicine.
2. Commonly used in Tamil Nadu tribes' traditional medicine to treat serious illnesses like fever, cough, diarrhea, gastroenteritis, skin conditions like candidiasis, urinary tract infections, and wound infections
3. Frequently used in diuretic and cardiotonic ayurvedic medicines.
4. It affects lengthy immunity and prevents aging.
5. It is thought to increase cancerous tumors and has been reported to cure blindness.

Chemical Composition:

The triterpenes, arjun glucoside I, arjun Genin, and the chebulosides I and II are among the glycosides that have been identified from Terminalia chebula. The phenolic compounds ellagic acid, chebulinic acid, gallic acid, ethyl gallate, punicalagin, terflavin A, terchebin, luteolin, and tannic acid are among the other ingredients. Chebulin is a coumarin conjugated with gallic acid. [5] [6] One phenolic acid component that was separated from the ripe fruits is chebulic acid. [7] [8] The bark can be used to separate luteic acid. [9] Terflavin B, a kind of tannin, is also present in T. chebula, and the fruits contain chebulinic acid. [10] Tannins, anthraquinones, chebulinic acids, chebulagic acid, chebulic acid, ellagic acid, and gallic acid are the fruits' main bioactive components.

Sorbitol, glucose, and corilagin are among the other trace amounts. Triterpene glycosides and polyphenolic substances. Other components of the fruits include carbohydrates, reducing sugars, and flavonoids.

Doses: 3–6 grams of powdered medication
Abhayarista, Agastya Haritaki Rasayana, Chitraka Haritaki, Danti Haritaki, Dashamula Haritaki, Danti Haritali, Brahma Rasayana, Abhaya Lavanaa, Pathyadilepa, and Triphala churna are important formulations.

Pharmacological Activity

1. Antioxidant & free radical scavenging activity

1. Terminalia chebula fruit showed antioxidant activity in six extracts and four compounds; the phenolic compound was identified to be the cause of this activity. [1]
2. It was discovered that phenolic compounds in Terminalia chebula's leaves, bark, and fruit were the cause of their strong antioxidant action. [2]
3. In the polyherbal formulation (Aller-7/NR-A2), Terminalia chebula prevented hemolysis caused by free radicals and also markedly reduced the generation of nitric oxide from lipopolysaccharide-stimulated murine macrophages. [3]
4. By examining the suppression of radiation-induced lipid peroxidation in rat liver microsomes at varying dosages, the aqueous extract of Terminalia chebula demonstrated strong antioxidant activity. [4]

In vitro, methanolic extract was also shown to scavenge superoxide and hydroxyl radicals and prevent the development of lipid peroxide. [5] Acetone extract has more antioxidant activity than alpha-tocopherol, and the principal phenolic compounds found in it were flavonol aglycones and their glycosides, hydroxybenzoic acid derivatives, and hydroxycinnamic acid derivatives, according to HPLC study using diode array detection. [6]

An analysis of the effects of extracts from five Iranian traditional medicinal plants—Quercus infectoria Olive, Terminalia chebula Retz, Lavendulastoechas L., Mentha longifolia L., and Rheum palmatum L.—on the scavenging of free radicals and the inhibition of mushroom tyrosinase activity. Tyrosinase activity and the DPPH radical were generally markedly decreased by Q. infectoria and T. chebula. Both tasks required concentration, although not in a straight path. Prior to doing additional testing and transferring to in vivo settings, the cytotoxicity of these plant extracts must be investigated in pigment cell culture. [7]

2. Cardioprotective activity

It was discovered that pretreatment with Terminalia chebula extract reduced the impact of isoproterenol on the production of lipid peroxide and preserved the activity of the diagnostic marker enzymes in rats with isoproterenol-induced cardiac injury. [8] In an isolated frog heart model, its pericarp has also been shown to exhibit cardioprotective properties. [8]

3. Antidiabetic and retinoprotective activity

1. In diabetic (Streptozotocin-induced) rats, a 44% decrease in the peak blood glucose at the second hour of the glucose tolerance test demonstrated that the water extract of dry Terminalia chebula fruits at a dose of 200 mg/kg body weight enhanced glucose tolerance. [9] In the rat model of metabolic syndrome, Terminalia chebula fruit extract significantly and dose-dependently lowers blood glucose levels. [10]
2. Terminalia chebula fruit and demonstrated radioprotective effects as well as a dose-dependent decrease in blood glucose in streptozotocin-induced diabetic mice in both short- and long-term studies. [11] [12]

4) Cytoprotective activity

The extract of the herbal remedy Kashi (Myrobalan, the fruit of Terminalia chebula) contained gallic acid (GA) and CA, which were identified as the active principals that inhibited the cytotoxic T-lymphocyte-mediated cytotoxicity. At comparable doses, GA and CA also prevented granule exocytosis in response to anti-CD3 stimulation. [13]

The HEK-N/F cells demonstrated a significant cytoprotective response to the ethanolic extract of Terminalia chebula fruit. Furthermore, its extract demonstrated a strong cytoprotective activity against oxidative damage caused by UV radiation. The Southern Blots of the terminal restriction fragments of DNA taken from the sub-culture passage demonstrated that Terminalia chebula extract inhibited the age-dependent shortening of telomere length, which was the reason for these observations. [14] It showed duodenal ulcer development and seemed to have a cytoprotective impact on the stomach mucosa in vivo. [15]

Its fruits have also been shown to have a cytoprotective impact against oxidative stress and an inhibitory effect on cellular aging. [16]

5) Antiviral activity

Fruits of Terminalia chebula provided three galloyl glucoses (IIIV), GA (I), and four immunodeficiency virus type 1 (HIV-1) integrase inhibitors. Their galloyl moiety is essential for inhibiting the compound's 3'-processing of HIV-1 integrase. [17] Terminalia chebula also inhibits retroviral reverse transcriptase. [18]

It supports its traditional usage to help in the recovery from acute respiratory infections by protecting epithelial cells against influenza A virus. [19]

Additionally, it showed both in vitro and in vivo therapeutic effectiveness against the herpes simplex virus. [20]

A group of Japanese researchers looked into the impact of T. chebula on human cytomegalovirus (CMV) as a result of these findings. They concluded that T. chebula may be helpful for preventing CMV disease and immunocompromised patients after finding that it was effective in preventing the replication of cytomegalovirus in vitro and in an AIDS model with immunosuppressed animals. [21] vi Additionally, it helps with AIDS and other sexually transmitted infections. [22] T. chebula tannins work well against potato virus X. [23]

6) Antiprotozoal activity

T. chebula and four other botanicals (Boerhavia diffusa, Berberis aristata, Tinospora cordifolia, and Zingiber officinale) showed antiamoebic activity against Entamoeba histolytica, with a maximum cure rate of 73% in experimental amoebic liver cure in hamsters [24] and 89% in experimental caecal amoebiasis in rats. [25] T. chebula seeds acetone extract exhibited anti-plasmodium capabilities against Plasmodium falciparum. [26]

7) Anti-inflammatory & anti-arthritic activity

By preventing the production of inducible nitric oxide, an aqueous extract of T. chebula's dried fruit demonstrated anti-inflammatory properties. [27] The development and progression of collagen-induced mice were markedly inhibited by chebulic acid derived from T. chebula immature seeds. [28] In rats with Freund's adjuvant-induced arthritis, Terminalia chebula in a polyherbal formulation (Aller-7) demonstrated a dose-dependent anti-inflammatory activity. [29]

8) Anti-allergic activity

Terminalia chebula was one of seven medicinal herbs that made up the polyherbal preparation Aller-7, which demonstrated strong antiallergic efficacy in vitro on an isolated guineapig ileum substrate. [30]

9) Anticarcinogenic activity

In a number of malignant cell lines, such as the human (MCF-7) and mouse (S115) breast cancer cell lines, the human osteosarcoma cell (PC-3), and a non-tumorigenic immortalized human prostrate cell line (PNT1A), ethanol extract of Terminalia chebula fruit inhibited cell proliferation and caused cell death in a dose-dependent manner. Additionally, components with promising anticarcinogenic activity are present in Terminalia chebula fruit powder and bark acetone extract. The fruits of Terminalia chebula Retz. yielded chebulagic acid, a COXLOX dual inhibitor that caused the COLO-205 cell line to undergo apoptosis. [31]

A team of researchers revealed that the phenolics in Terminalia chebula Retz fruit inhibited cell growth. They discovered that the most growth-inhibiting phenolics in T. chebula were ellagic acid, tannic acid, and chebulinic acid. [32]

10) Antispasmodic activity

One of Terminalia chebula's many research showed that it has "anti-vata" or antispasmodic qualities by lowering abnormal blood pressure and intestinal spasms. This supports its long-standing benefits for intestinal diseases, including spastic colon. [33]

11) Wound healing activity

When an alcoholic extract of Terminalia chebula leaves was applied topically to rat dermal wounds, the wounds healed more quickly than salivary bacterial wounds for up to 90 minutes after rinsing. [34]

12) Immunomodulatory activity

In golden hamsters with experimental amoebic liver abscess, Terminalia chebula crude extract boosted the cell-mediated immune response [35]. In mice, Terminalia chebula aqueous extract increased humoral antibody titre and caused a delayed form of hypersensitivity. [36]

13) Adaptogenic & antianaphylactic activity

Terminalia chebula's water-soluble fractions significantly increased the synthesis of anti-dinitrophenyl IgE-induced tumor necrosis factor alpha from rat peritoneal mast cells, suggesting that it has a potent antianaphylactic activity. [37]

Additionally, research on animals demonstrated that T. chebula extract had a considerable antianaphylactic effect by lowering serum histamine levels after inducing anaphylactic shock. [38]

Animals were given six Ayurvedic herbs to assess their adaptogenic potential, including T. chebula fruit. In different ways, each of the six traditional Rasayana plants helped the animals cope with a range of stressors.

14) Antifungal activity

A Terminalia chebula aqueous extract shown antifungal properties against several yeasts and dermatophytes. [39] [40]

It works well against the dermatophytes Epidermophyton, Floccosum, Microsporum gypseum, and Trichophyton rubrum as well as the pathogenic yeast Candida albicans. [41]

It has also been shown to have inhibitory effects on three yeasts (Candida spp.) and three dermatophytes (Trichophyton spp.). [42]

15) Hypolipidemic/ Hypocholesterolemic activity

Terminalia chebula extract has been shown to have hypolipidemic effect against experimentally generated atherosclerosis. [43]

16) Gastrointestinal motility improving and antiulcerogenic activity

The fruit of Terminalia chebula has been proven to lengthen the time it takes for the stomach to empty, despite its long-standing traditional use as a laxative. [44] The improvement in the secretory condition of Brunner's gland, which is implicated in the prevention of duodenal ulcers, seems to balance this action with a protective impact on the gastrointestinal mucosa. [45]

17) Antiamoebic activity

The highest rates of experimental amoebic liver abscess in hamsters were 73% when Terminalia chebula was combined with four other botanicals (Boerhaviadiffusa, Berberis aristate, Tinospora cordifolia, and Zingiber officinale) [46], and experimental caecal humoral antibody (HA) titre and delayed type hypersensitivity (DTH) in mice were 89% [47].

18) Chemo preventive activity

 In male Wistar rats, Terminalia chebula had a chemopreventive impact on the oxidative stress, toxicity, and cell proliferation response caused by nickel chloride. [48]

19) Radioprotective activity

When Terminalia chebula extract was given to mice before they were exposed to radiation throughout their bodies, the perioxidation of membrane lipids in the mice's liver decreased, and radiation-induced DNA damage was also lessened. Additionally, it shielded human lymphocytes against the damage that gamma radiation causes to DNA when exposed in vitro. [49]

20) Hepatoprotective activity

T. chebula fruit extract's hepatoprotective properties were examined in various animals whose livers had been damaged by iron-dextran injection [50], 2-acetylaminofluorene [51], ethanol administration [52], and anti-tuberculosis medication (a combination of rifampicin, isoniazid, and pyrazinamide) [53].

21) Anti-spermatogenic activity

By decreasing the length of the germinal epithelium, the number of germ cells, the weight of the reproductive organs, and the diameter of the stage VII tubules, a recent study revealed the plant's anti-androgenic qualities. As a result, creating male contraceptives might be advantageous [54]. Additionally, a polyherbal preparation that contained T. chebula extract was revealed to have lessened testicular action by lowering the level of semi logical and androgenic sensors in experimental mice [55].

CONCLUSION

In most parts of Africa, Tridax procumbens is considered a weed and is well-known for its pharmacological properties. The plant has a wide range of uses, including pharmacological, hepatoprotective, immunomodulatory, wound-healing, antidiabetic, antibacterial, anti-inflammatory, and antioxidant properties, as well as treatment for bronchial catarrh, diarrhea, and dysentery. Biomolecules including anthraquinone, catechol, flavonoids, phenolic compounds, saponins, steroids, tannins, and terpenoids were found during analysis.

Various extracts have been used to treat various illnesses and isolate metabolites. Many of the extraction studies that were examined in the reviewed literature lacked confirmatory research, and some of the investigations contradicted one another. Numerous extraction techniques seem to have some beneficial effects on a range of illnesses. When compared to traditional treatment, data shows that Tridax has a positive anti-diabetic impact.

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