Trichodesma Indicum / Adhapushpi  (Sanskrit) / Andhaphuli or Chhotta Kalpa (Hindi)

General features: The botanical name is Trichodesma indicum (TI), an Ayurvedic plant (Adhapushpi in Sanskrit), which belongs to the Boraginaceae family of the Trichodesma genus. In English, it is called Indian Borage or Blue Hound’s tongue. It is a widely famed Ayurvedic/medicinal plant in the Indian subcontinent and in many Southeast Asian nations, often used for therapeutic benefits without any significant nutritional content. It is also considered to be an adaptogen. Despite its eminent medicinal role, the plant has been characterized as a weed. In India, it is mainly found in the sub-tropical Himalayan regions and Western Ghats of Maharashtra and Karnataka at about 5000 ft high altitude. It is also distributed in Afghanistan, Pakistan, Myanmar, the Philippines, and Mauritius. TI is an erect, spreading, branched annual herb about ~ 1.7 ft tall with hairy tubercles, which mostly grows in stony wasteland with semi-arid/ less watery ground. The leaves are stalkless, lance-shaped, opposite, 1 – 6 inches long, with a pointed tip and heart-shaped base. The flower grows singly in the leaf axils. The sepal tube is green and hairy, ~ 1.0 inch long. The flowers are pale blue, pink, or white and ~ less than an inch in diameter with pointed petals. The fruits are ellipsoid and enclosed by the sepals. The nutlets are tiny, ~ 0.2 inches long, and rough on the inner surface. The flowers grow in August, and thereafter, fruits appear in October. [1,2]. It is an edible plant with a bitter taste. Numerous studies have established that TI / Adhapushpi has versatile medicinal or beneficial roles in health. Regarding the use as traditional medicine in rural communities, it offers antimicrobial, antiinflammatory, and antidiarrheal activities. The plant is fairly non-toxic and is thus safe to use in appropriate situations. It also treats fever and infections [1].

Traditional uses: The plant, TI/Adhapushpi, possesses an extensive history in Ayurveda, displaying versatile uses as a folk medicine, particularly against rheumatic arthritis, infections, and inflammatory diseases. It also offers a carminative effect. Additionally, it has an abortive role and is effective in reducing dysmenorrhea, the contraction of the uterine muscle due to excessive prostaglandin production. The plant parts, such as leaves, stems, and flowers, or even the entire plant, are often used for treatment. In rural areas, TI protects people from intestinal infections. Uniquely, it helps treat Irritable Bowel Syndrome (IBS), a debilitating inflammatory autoimmune disease. TI acts against it, possibly due to its anti-inflammatory behavior, providing relief in the case of inflammation and associated pain, also exerting an analgesic action. [https://dravinashtank.in/food-nutrition/adhapushpi-trichodesma-indicum-amazing-facts-nutritional-value-health-benefits-side-effects/.].The plant even helps improve cognitive functions and subsequently enhances memory. It has a beneficial role on cardiovascular health, enabling it to control cardiac problems and irregularities. Furthermore, it is fairly non-toxic, at least at low doses [3]. In Andhra Pradesh of India, the roots of TI are used to treat rheumatic arthritis. In Tamil Nadu, the leaf juice is often applied externally to treat earaches or for healing wounds. On many occasions, the whole plant extract is used to cure influenza and cough. However, it is majorly used for dysentery, arthritis, arthralgia, and joint pain. The extract of plant parts has shown antioxidant, antitussive, antidiabetic, anti-inflammatory, diuretic, antimicrobial, and antifungal effects [4,5]. Historically, the leaves were used as a traditional medicine to cure a few cancers.  The recent studies in vitro have shown that they exert antiproliferative and antimitotic activities against several cancer cells, validating the anticancer potential [6]. TI mostly offers antifungal, antitussive, antidiabetic, antimicrobial, diuretic, and metal chelating activities [4].

Uses as Folk Medicine in India

Plant partsUsesPlace of Use in India
RootsReduction of swelling and Bodyache, dysentery, and fever.Chota Nagpur and Kandhamal District of Orissa.
LeavesHealing wounds, cuts, earache,  and preventing bleeding. Kandhamal District of Orissa And a few regions in Tamil Nadu.
Fresh leavesCuring stomach upset and  Diarrhea/dysentery in children.Tiruchirappalli, Tamil Nadu.
Leaves + RootsCuring and preventing tumors Growth, urinary problems, and Snake bite.Chhattisgarh.

Phytochemicals and associated medicinal actions: The basic phytochemical screening of the methanolic extract has shown the existence of different secondary metabolites such as alkaloids, flavonoids, saponins, steroidal compounds, tannins, and phenolic compounds, whereas the aqueous extract shows the presence of alkaloids, flavonoids, tannins, saponins, and steroids, including a few amino acids and minerals [7].

Major Phytocomponents

Compound categoryCompounds
AlkaloidsMonocrotaline, Supinine
SteroidsStigmasterol, β-sitosterol
Terpenoidsα-Amyrin, Lupeol
Fatty acids and estersOleic acid, linoleic acid, linolenic acid, palmitic acid, Stearic acid, n-decyl laurate, n-tetradecanyl laurate, n-nonacosanyl palmitate, lanast-5-en-3β-D-glucopyranosyl-21(24)-olide, stigmast-5-en-3β-ol-21(24)-olide.
Aliphatic hydrocarbons And ketonesHexacosane, n-pentacos-9-one, n-dotriacont-9-one-13-ene,
Tannins 

Analysis has shown that the identifiable major alkaloids are monocrotolin and suspinine, lycopsamine, echimidine, and intermedine, which are categorized as pyrrolizidine alkaloids, whereas the other non-alkaloid components are hexacosane, amylin, lupeol, β-sitosterol, stigmasterol, catechin, gallic acid, chlorogenic acid, ferulic acid, caffeic acid, cinnamic acid, myricetin, and quercetin [6]. The pyrrolizidine alkaloids monocrotalin, supinine, lycopsamine, and intermedine are known to cause hepatotoxicity. Monocrotolin even shows an adverse role on the lungs and kidneys. It is even considered to be a cancer-causing agent in humans and animals. Additionally, it enhances the urea level in blood. Acting on calcium sensing receptor (CaSR), it damages endothelial cell walls in the lungs, inducing pulmonary hypertension [8]. It causes DNA damage and induces apoptosis in brain astrocytes [9]. On the other hand, supinine acts as a potent anti-inflammatory drug and also has antimicrobial activity. It exerts bronchodilation, therefore effective in treating respiratory problems like allergies, asthma, or the common cold [10]. It shows antioxidant behavior, protecting cells from oxidative stress. Lycopsamine and Intermedine display almost identical behavior, exerting both toxic as well as protective roles. Although these compounds are hepatotoxic, they exhibit significant anti-inflammatory properties by enhancing IL-10 (anti-inflammatory cytokine) expression and inhibiting TNF-α generation. Additionally, they exhibit anticancer activity, particularly against lung cancer, through mechanisms such as apoptosis induction and IL-2 expression inhibition [11].  The health effects of phenolic acids are widely acclaimed. They are readily absorbed via the intestinal wall and act as antioxidants, reducing oxidative stress, thereby lowering the risks of numerous metabolic diseases like cancers, diabetes, and cardiovascular problems. The antioxidant effect relies on singlet oxygen quenching; also, the resonance-stabilized aromatic moiety causing H-atom donation, resulting in an antioxidant action via the radical scavenging event. Its potential beneficial health effects are documented [12]. TI  synthesizes several flavonoids like catechin, myricetin, and quercetin, which offer a number of medicinal benefits, acting as anti-inflammatory, anticancer, antioxidant, and anti-viral agents. Their effectiveness as well as the working mechanism have already been established. They have even shown neuroprotective and cardioprotective behavior [13,14,15]. Recent studies have found a strong link between flavonoid intake and the reduction of the risks of Alzheimer’s and related dementia [15]. The role of oleic, linoleic, and similar unsaturated fatty acids is well-known. They are beneficial and crucial to maintain overall health. They can reduce inflammation, improve blood cholesterol levels, lower the risk of cardiovascular problems, and maintain the structural integrity of the cell surface membrane [16]. The leaves contain moderate levels of tannins. Tannins are macromolecular polyphenols. They often help protect against chronic diseases, reducing inflammation, oxidative stress, and combating infections. Tannins are also beneficial to cardiovascular health and have anticancer and digestive health-promoting effects, also preventing diarrhea. The effects are speculated to be due to their antioxidant and related biochemical actions [17].

Pharmacological effects: Numerous versatile effects of TI have been observed in human health for a long time. A few of them are described below.

Antipyretic and analgesic activity – Studies indicate that the ethanolic extract of the plant produces antipyretic and analgesic effects. The dose-dependent administration of (100, 200, and 400 mg/Kg) of the extract shows significant inhibition of acetic acid-induced abnormal constrictions in mice. The body temperature is reduced for nearly three hours. This extract also reduces yeast-induced pyrexia for about four hours. The presence of tannins, terpenoids, steroids, flavonoids, and saponins is identified as a liable ingredient behind the analgesic and antipyretic actions [18].

Anti-inflammatory effect – The chloroform extract of the TI root shows dose-dependent (50 to 200 mg/Kg) strong anti-inflammatory behavior against edema created by carrageenan, dextran, histamine, and serotonin, as well as against the induction of tissue granulation by cotton pellet in laboratory rats. The effect has been compared with the standard medications like dexamethasone, cyproheptadine, and indomethacin. In all cases, significant anti-inflammatory effects are observed. In the case of granuloma weight, the extract the effects are more pronounced than indomethacin or dexamethasone [19]. The leaf extract by hexane, methanol, and water is tested for anti-inflammatory activity using the 5-Lipooxygenase assay in vitro and rat paw edema induced by carrageenan in vivo. In the case of in vivo experiments, the extract shows significant inhibition with incremental doses of 200 mg/Kg (IC50 = 55.62%) and 400 mg/Kg (IC50 = 71.43%) (p<0.01) [20]. The anti-inflammatory effects of flower extract by ethanol have also been evaluated. It has been noted that terpenoids, steroids, and flavonoids can exert membrane lysis activity. The action is more effective in the case of methanolic extraction [21].

Antidiabetic effect – Experiments conducted in vitro, α-amylase assay, and in vivo streptozotocin-nicotinamide-induced type-2 diabetic rat using extractions of four different solvents, hexane, acetone, methanol, and water, showed significant antidiabetic activity. The in vitro amylase activity and glucose uptake have been tested on yeast cells. All four extracts have indicated a decline in blood glucose levels in streptozotocin-nicotinamide-induced type 2 diabetic animals. In a way, it has been established that TI exhibits potent antidiabetic activity in the case of type 2 diabetes. The effect is comparable to that of glibenclamide, and methanol stands out as the most effective solvent for the efficient extraction process applicable to diabetes [22]. The liable ingredients are alkaloids, glycosides, flavonoids, saponins, and steroids.

Antitussive effect – The methanolic extract of the entire plant has been tested against sulfur dioxide-induced cough reflex in Swiss albino mice. The extract shows significant inhibition in the frequency of coughing when compared to the standard drug codeine phosphate. The results have reestablished its traditional use to treat coughing [23].

Antimitotic and antiproliferative effect – The study has been carried out using the aerial parts of the plant. The antimitotic activity is carried out in vitro by following the usual assay procedure using Allium cepa (onion) root tips [24]. The antiproliferative assay is conducted using a yeast model and several human cancer cell lines, MCF-7 (breast cancer), HOP (cardiomyocytes), MOLT-4 (human lymphoblast), HCT-15 (colorectal cancer), and PRO (Chinese hamster ovarian cells). The significant antimitotic and antiproliferative activities are noticed, which are comparable to methotrexate, vincristine, and Adriamycin. The highest inhibition is observed against MCF-7 and MOLT-4. The identifiable components are β-sitosterol, catechin, and gallic acid. So, as directed by the traditional use, TI has the potential to cure or prevent cancers [25].

Diuretic effect – The aqueous or methanolic extract (300 mg/Kg) of the aerial parts is used for the study by following the Lipschitz model, which has been evaluated by measuring the urine volume, showing the Lipschitz value ~ 1.25, compared with the standard. The potassium level in urine is seen to be high in the case of aqueous extract. Contrarily, sodium concentration is higher in the case of the methanolic extract. It is quite evident that the phytocompounds in TI have a diuretic property [26].

Antimicrobial effect – To study the antimicrobial effect of the ethanolic root extract and its isolated components, the disc diffusion method has been followed while assessing the minimal inhibitory concentrations as well as the minimal bactericidal or fungicidal concentrations. The isolated compounds are the esters of long-chain fatty acids or tetra cyclic triterpenes; n-tetradecanyllaurate, n- n-decanoyllaurate, stigmast-5-en-3b-ol-21 (24)-olide, n-pentacos-9-one, n-nonacosanylpalmitate, n-dotriacont-9- one-13-ene, lanast-5-en-3b-D-glucopyranosyl-21(24)- olide, and stigmast-5-en-3b-ol-23-one. They have shown varying degrees of efficiency. Among them lanast-5-en-3b-D-glucopyranosyl 21(24)-olide shows the most potent activity, particularly against S. aureus (MIC ~ 2.4 mg/ml). The ethanol extract of the whole plant has exhibited a strong antimicrobial effect against S aureus, B. subtilis, and C albicans with MIC ~ 19.2 mg/ml. indicating its potent antibacterial role [27]. Extracts of leaves and aerial parts, obtained by various methods of solvent extractions, exhibit antibacterial activity to varying degrees. The methanolic leaf extract, which exhibits greater potency, contains approximately twenty different compounds, which include alkaloids, flavonoids, tannins, and reducing sugars, thereby justifying the plant’s traditional use [28].

Anti-arthritic effect – Studies have shown TI extracts can exert strong anti-inflammatory/anti-arthritic effects, thereby potently able to manage arthritis. In vitro studies on mouse macrophages have demonstrated that extracts from various plant parts can inhibit or prevent the production pathways of pro-inflammatory cytokines, particularly prostaglandins, TNF-α, and NO, which are involved in the inflammatory response associated with arthritis.  Seemingly, the notable anti-inflammatory components are alkaloids, flavonoids, phenolics, tannins, and steroids. Molecular docking and computational In Silico studies have further established the therapeutic potential of those compounds in arthritis [29].

Miscellaneous activities of TI – 1) Insecticidal and herbicidal activity. 2) Anti-irritant and anti-sting activity. 3) Anti-diarrheal activity. 4) Antispasmodic activity. 5) Antiparasitic activity. 6) Anti-infection activity. 7) Corrosion inhibition activity. 8) Metal chelating activity [5,30].

Hepatotoxicity: The study on toxicity is carried out by using the aqueous methanolic extract of the whole plant in mice. The LD50 of the extract is found to be greater than 4000 mg/Kg. Below that level, no significant changes are observed regarding the liver enzymes or bilirubin, albumin, or globulins. Necrosis and excessive vacuolation have been noticed only for maximum doses under histopathological observation, indicating hepatoxicity and mild liver injury [31].

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