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Careya arborea / Kumbhi (Bengali)/ Sthalakumbhi (Hindi)/ Kalindi (Sanskrit)

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General features: Careya arborea (CA) is a tropical deciduous medicinal tree native to the Indian subcontinent, Afghanistan, and Indonesia. It is commonly known as wild guava, Ceylon oak, or Patna oak in English; Vakamba in Bengali; kalindii in Sanskrit; and Kumbhi in Hindi. The species belongs to the genus Careya in the family Lecythidaceae. It grows to about 50 feet and develops a broad, dense, dark crown. Its grey-brown bark peels away in papery flakes. Broad, obovate leaves, 6–8 inches long, cluster at the branch tips and turn reddish bronze in cold weather before falling. The fragrant, short-lived spring flowers bear numerous delicate, brush-like stamens that are white with yellowish tips and pink-red bases. The tree produces spherical green berries or drupes, 1.5–2 inches in diameter, with persistent calyx segments at the top. Their resemblance to guavas gives the plant its common name, “wild guava.” The fruits are edible, although the seeds are slightly poisonous [1,2]. In early colonial times, the dried bark was used in matchlocks. In Myanmar, the leaves are used to roll cheroots or fermented with tea leaves to make drinks, while fresh young leaves and flowers are eaten in salads in Myanmar, Thailand, and Laos. In traditional Ayurvedic medicine, an astringent bark decoction was taken for digestive disorders, diarrhea, dysentery, and coughs, while poultices of crushed leaves were applied to wounds and skin rashes to support healing [3]. No adverse effects have been reported for its use.

History of CA Uses: The medicinal use of Careya arborea (CA) has been documented in the ancient Ayurvedic texts Charaka Samhita and Sushruta Samhita. Valued for its astringent properties, the plant was traditionally believed to balance the Kapha and Pitta doshas [3]. English botanist William Roxburgh named the genus in honor of William Carey (1761–1834), a missionary, orientalist, and botanist based in Serampore, India, who established the Agri-Horticultural Society of India. During British colonial rule, the slow-burning, fibrous inner bark was processed for use in matchlocks. Ayurvedic and folk practitioners have used CA to treat gastrointestinal disorders, ulcers, wounds, and bedsores. In parts of India, it has also been added to postpartum baths to relieve fatigue and jaundice after childbirth [4]. Over time, CA spread to Myanmar, Thailand, the Malay Archipelago, and neighboring regions, where it acquired different local names. Roxburgh also recorded its use by tribal communities in Odisha to manage dyspepsia. In Karnataka and Maharashtra, its branches were used in village ceremonies to ward off evil spirits, and the plant remains important to several tribal communities. Modern Ayurvedic schools combine it with licorice and triphala, while commercial preparations market it as a multipurpose tonic rather than solely as an antidiarrheal remedy. During a 19th-century cholera outbreak in Kolkata, local physicians reportedly administered CA decoctions to limit fluid loss, possibly because of the plant’s high tannin content. Its progress from sacred temple grounds to clinical use reflects a long history of adaptation across diverse medicinal practices [3].

Traditional or Folk medicinal use: CA is traditionally used to treat a wide range of ailments. Various decoctions address gastrointestinal disorders such as diarrhea and amebic dysentery and help reduce fluid loss, tissue bleeding, and intestinal inflammation [3]. Young shoots serve as mild carminatives to stimulate appetite and ease colic. Preparations made from fragrant flowers or cold-pressed seed oil act as expectorants for coughs, bronchitis, chronic asthma, and sore throats, while mucilage-based emollients soothe respiratory irritation. Bark paste is applied to skin irritation, itching, eczema, ringworm, insect bites, and eruptive fevers [5]. Leaf paste is used topically for wounds, ulcers, abscesses, and burns. In parts of southern and central India, inner-bark infusions are taken for analgesic and antipyretic effects, including to manage malarial fevers and reduce rheumatic joint pain, swelling, and inflammation [6].

Phytochemicals and medicinal actions: CA synthesizes versatile bioactive phytochemicals that can exert numerous physiological activities, adding many therapeutic claims. The bioactive components are broadly categorized as triterpenoids and sapogenins, phenolics, tannins, flavonoids, sterols, and saponins, which are differentially distributed in plant parts. Below is a brief statement of their relative distribution [7].

Distribution of different categories of phytochemicals in Careya arborea CA

Plant partsCategory -1Category – 2Category – 3Category – 4Cardiac glycosides
RootsPhenolics & Flavonoids (High)Tannins & Saponins (Low)Alkaloids (High)Terpenoids & Sterols (High)None or very little.
Stems and BarksPhenolics & Flavonoids (High)Tannins & Saponins (High)Alkaloids (High)Terpenoids & Sterols (High)Cardiac glycosides (High)
LeavesPhenolics & FlavonoidsTannins & Saponins (Low)Alkaloids (Low)Terpenoids & Sterols (High)Cardiac glycosides (High)
FruitsPhenolics & Flavonoids (High)Tannins & Saponins (Low)Alkaloids (Low)Terpenoids & Sterols (High)Cardiac glycosides (Low)
SeedsPhenolics & Flavonoids (High)Tannins & Saponins (Low)Alkaloids (Low)Terpenoids (Low)Cardiac glycosides (High)
FlowersPhenolics & Flavonoids (High)Tannins & Saponins (High) Triterpenoids & Sterols (High) 

The analysis indicates numerous categories of bioactive chemicals in stem bark extracts. The major components are the pentacyclic triterpenes lupeol, β-sitosterol, and betulinic acid, as well as a unique piperidine derivative alkaloid.

Lupeol, betulin, and betulinic acid are lupane-type pentacyclic triterpenoids with significant medicinal potential. All are multitarget therapeutic agents that can regulate NF-κB signaling-mediated inflammatory pathways as well as Nrf2-modulated antioxidant defense [8,9].

Fruits contain gallic acid and 3,4-dihydroxybenzoic acid, quercetin-3-O-glucopyranosyl-glucopyranoside, and quercetin 3-O-(6-glucopyranosyl)-glucopyranoside, isolated from the ethyl acetate and dichloromethane extracts of CA fruits [7]. As usual, these flavonoids and their glycoconjugates have diverse beneficial roles, acting as antioxidants, anti-inflammatory, and neuroprotective agents [10].

The most notable seed components are phytosterols like α-spinasterone and α-spinasterol, and a few triterpenoids like 16-desoxy barringtogenol C, barringtogenol C, and barringtogenol D. They also act as strong anti-inflammatory and analgesic agents, provide neuroprotection, and act as antidepressants [11]. On the other hand, barringtogenol isomers are traditionally used to treat malaria and skin diseases or wounds [12].

Acid hydrolysis followed by ethanol extraction provides the triterpenoid lactone careyagenolide, Maslinic acid, and 2α-hydroxy ursolic acid. In contrast, extraction with methanol shows the triterpenoid saponins arborenin and desacylescin III [13].

CA produces the pentacyclic triterpenoids careyagenolide, maslinic acid, arborenin, and desacylescin III primarily in its leaves; all have demonstrated potential health benefits [14]. Maslinic acid, the most extensively studied, has anti-inflammatory and chemopreventive activity. It inhibits cancer-cell proliferation, induces apoptosis in colon and gastric cancer cells, and suppresses tumor growth [15]. As a glycogen phosphorylase inhibitor, it also helps regulate blood glucose, reduce insulin resistance, and counter high-fat-diet-induced adiposity [16]. In addition, maslinic acid reduces inflammation by inhibiting NF-κβ signaling and may protect brain cells during ischemia or stroke by limiting oxidative stress and glutamate toxicity [17]. Ursolic acid, another well-known pentacyclic triterpene, offers several potential benefits. It promotes skeletal-muscle growth and strength while downregulating genes associated with muscle atrophy [18]. It also reduces liver fibrosis and fat accumulation, protects the heart from ischemic injury, slows vascular plaque progression, and induces apoptosis in several cancer-cell types through caspase activation [18]. Arborenin has notable antiparasitic activity, particularly against Leishmania donovani, the parasite that causes leishmaniasis [13]. Careyagenolide, a triterpene lactone, acts as a central nervous system depressant and has antimicrobial and antioxidant properties [19]. Desacylescin III, isolated mainly from leaves, is an escin-family saponin with anti-inflammatory, vasoconstrictive, and vasoprotective effects, as well as notable antitumor activity in laboratory studies [20]. There are also a few other ingredients that have been isolated, which are Taraxerol, ellagic acid, n-hexacosanol, quercetin, β-sitosterol, careaborin, and tannins.

Taraxerol has broad medicinal potential as a potent anti-inflammatory, antioxidant, neuroprotective, and anticancer agent [21]. Careborin, an important pharmacological constituent of CA, is a pentacyclic triterpene ester found mainly in the leaves. It exhibits strong antimicrobial activity against pathogens such as Staphylococcus aureus and Escherichia coli [22]. As a derivative of Taraxerol, Careborin also scavenges free radicals, thereby reducing oxidative stress and inflammation. These properties may help explain the traditional Ayurvedic use of CA leaves and bark for diarrhea, skin ulcers, localized inflammation, tumors, and colds [23]. Ellagic acid, β-sitosterol, and quercetin are diverse categories of compounds. Ellagic acid is a polyphenol, quercetin is a flavonoid, and β-sitosterol is a phytosterol. Ellagic acid is a powerful free radical scavenger, metal chelator, and gut microbiome modulator. It is metabolized by the intestinal microbiome to form a possible therapeutic ingredient, urolithin [24]. In general, they offer anti-inflammatory, hepatoprotective, neuroprotective, anticancer, and antidiabetic actions, also providing cardioprotective effects. β-sitosterol is particularly effective in maintaining prostate health, so often used in treating benign prostatic hyperplasia [25]. Tannins are polyphenolic compounds and have numerous activities, such as wound healing, forming a protective layer on damaged skin or tissues, keeping away from bacteria, and promoting regeneration of new tissues [26].

Piperidine derivatives and alkaloids have diverse pharmacological actions, particularly in treating cognitive and mental health disorders [27]. In addition to their role in pain management, some exert antipsychotic and antidepressant effects through anticholinergic activity and monoamine oxidase inhibition, suggesting potential applications in Alzheimer’s disease and other neurodegenerative disorders [28]. Some also act as nootropics and stimulants and are therefore used in the treatment of ADHD [29].

Pharmacological effects: Studies have shown that different plant parts have versatile pharmacological roles, described below.

Anti-inflammatory effects – Leaves and stem bark contain high levels of betulinic acid and quercetin and its derivatives, which may be responsible for this effect. The extracts downregulate pro-inflammatory cytokines, such as TNF-α and IL-1β, and subsequently reduce malondialdehyde, C-reactive protein, and NO levels, which have been observed in carrageenan-induced edema in laboratory animals [30].

Antioxidant effects – The bark and fruit extracts, enriched with phenolics, gallic acid, rutins, chlorogenic acid, and tannins, are mostly liable for the effect. The methanolic and aqueous extracts have shown strong antioxidant properties. They can significantly scavenge free radicals such as DPPH, NO, and superoxide, helping protect tissues from oxidative stress [31]

.Anticancer and cytotoxic effects – Stem-bark extracts show notable anticancer and cytotoxic activity, likely because they are rich in phenolics, terpenes, sterols, tannins, and saponins. They induce apoptosis and inhibit tumor-cell proliferation [32]. Apoptosis may involve caspase-3 activation by phenolic compounds such as quercetin and gallic acid, while saponins and coumaroyl lupendioic acid may suppress cell division and colony formation in aggressive cancer cells [32]. Leaf extract also inhibits MCF-7 breast-cancer cell migration and downregulates MMP2 and MMP9 expression, suggesting potential value in breast-cancer prevention and treatment [33]. In addition, aqueous and ethanolic extracts inhibit growth, induce apoptosis, and reduce migration in HeLa cervical-cancer cells [34].

Hepatoprotective effects – Methanolic stem-bark extract demonstrated dose-dependent hepatoprotective activity in Wistar albino rats with CCl4-induced liver injury. Investigators assessed GPT, GOT, ALP, bilirubin, uric acid, and total protein, along with catalase, SOD, GSH, and vitamins C and E. Treatment reduced bilirubin, uric acid, and lipid peroxidation while increasing SOD, CAT, GSH, and vitamins C and E, confirming its hepatoprotective effect [35].

Antidiabetic effects – CA extracts may help control hyperglycemia by inhibiting key carbohydrate-metabolizing enzymes, limiting oxidative stress, and correcting diabetes-related lipid disturbances, consistent with their traditional antidiabetic use [36]. In diabetic rats, methanolic leaf extract potently inhibited α-glucosidase (IC50 ≈ 0.13 µg/mL); stem-bark extract was less active, achieving 43.5% inhibition [37]. The extracts also demonstrated hypolipidemic activity: 21 days of treatment significantly reduced total cholesterol and triglycerides, potentially lowering diabetes-associated cardiovascular risk [38].

Anticoagulant effects – Methanolic fruit and stem-bark extracts show significant anticoagulant activity by affecting both the intrinsic and extrinsic pathways in the coagulation cascade, with effects comparable to warfarin [39]. Identified active compounds include gallic acid, 3,4-dihydroxybenzoic acid, quercetin 3-O-glucopyranoside, and kaempferol 3-O-glucopyranoside. Because of this antithrombotic activity, CA may have potential as an alternative treatment for deep-vein thrombosis or pulmonary embolism [40]. The extracts lower the levels of clotting factors VIII, IX, XI, XII, and prekallikrein, delaying intrinsic pathways. Simultaneously, it also significantly increases prothrombin and thrombin time, thereby delaying the extrinsic pathway [39].

Antidepressant effects – Animal studies suggest that methanolic stem-bark extract produces sedative and general central nervous system (CNS) depressant effects rather than a selective antidepressant action [41,42]. Reported effects include reduced locomotor activity and a moderate decline in responsiveness to auditory and tactile stimuli [42]. CA has also been used traditionally to treat epileptic seizures. These neurological effects may involve several phytochemicals, particularly careyagenolide, maslinic acid, and ursolic acid [43].

Antifertility effects – Laboratory studies indicate that methanolic CA root extract produces potent but reversible antifertility effects in female animal models. Phenolic and phytoestrogenic compounds may mediate these effects by disrupting reproductive hormone cycles [44]. The extract markedly alters normal estrous-cycle patterns and inhibits pregnancy. In ovariectomized animals, its estrogenic activity mimics 17β-estradiol (E2), producing persistent estrus, likely because of its phytoestrogen content. Normal fertility returns after discontinuing treatment [45].

Antiulcer activity – In Ayurveda or folk traditional medicine, CA has been ascribed as an antiulcerative and gastroprotective agent. Recent laboratory studies have confirmed this role, particularly using the ethanolic extracts of leaves and stem bark in ulcerative rats [46]. The actions are mediated by the combined roles of cytoprotective, antisecretory, and antioxidant pathways. The extract efficiently reduces gastric juice volume and the activity of the H+/K+-ATPase proton pump responsible for stomach acid secretion [46]. In addition, it significantly enhances gastric wall mucus production, strengthening and protecting the stomach’s defensive lining from gastric acid [47]. Further protection is provided by the antioxidant and free-radical scavenging actions of the extract [46].

Antimicrobial and antiparasitic effects – CA has demonstrated antibacterial and antiparasitic activity, particularly against helminths, consistent with its traditional use in Ayurveda. These effects are attributed to bioactive compounds such as tannins, flavonoids, saponins, and terpenoids [48]. Laboratory studies indicate that extracts from the roots, stem bark, leaves, and fruits can disrupt the membranes of pathogenic bacteria and parasites and help expel intestinal helminths. Ethyl acetate extracts have also shown antileishmanial activity, suggesting potential for further investigation against protozoal infections [49,50]. Mechanistically, tannins may bind to bacterial cell walls and damage the outer membrane, while saponins increase membrane permeability. Phenolics and flavonoids may further support antimicrobial defenses by reducing infection-related oxidative stress [51].

Wound-healing effect – CA extracts have been shown to accelerate wound healing and tissue repair. Bark and leaf extracts are more active than other plant parts in promoting wound contraction and simultaneous cellular regeneration. The effect is particularly pronounced for burn wounds and often outperforms commercial medications [52]. Studies on molecular targets align with several cellular signaling pathways associated with TNF-α, PI3K-Akt, MAPK, and EGFR. The action accelerates fibroblast activity, angiogenesis, collagen formation, and epidermal regeneration. In burn wounds, topical application achieved a contraction rate of 98.53%, compared with commercial drugs like silver sulfadiazine (06.48%) [52].

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