Gen info
• Pavetta is a genus of flowering plants in the family Rubiaceae, comprising about 360 species of trees, evergreen shrubs, and sub-shrubs.
• Pavetta has small, white, tubular flowers sometimes salviform or funnel-shaped with 4 spreading petal lobes. Flowers are carried on terminal corymbs or cymes. (35)
• Genus was first established by Carl Linnaeus in Species Plantarum in 1753. Its early broad classification has undergone revisions refining its circumscriptions. In the early 1980s, systematic studies by Elmar Robbrecht's further clarified the genus. Recent estimates recognize about 350 species. (36)
• Etymology: The genus name Pavetta was establish by Linnaeus in 1753 in his Species Plantarum, where he described Pavetta indica as the type species based on specimens from India. The genus name derives from pawatta, a Sinhalese (Sri Lankan) name for a small tree in the genus. Alternatively, it may have derived from the Tamil word "pavaddai," meaning "skirt," referring to the plant's foliage or growth habit. And, still, another alternative derivation, from Malabar, India, deriving from the Latin pavimentum (pavement), evoking the mosaic-like patter of bacterial nodules visible on the leaves under certain conditions. (36) Indica is a Latin adjective meaning India, referring to where the species was first discovered or being native to the Indian subcontinent.
• Controversy: While P. indica is often cited in Philippine literature, some botanical studies suggest the true P. indica is confined to India and Sri Lanka.

Botany
• Gusokan is an erect, nearly smooth or somewhat hairy shrub, growing to a height of 2 to 4 meters. Leaves are elliptic-oblong to elliptic-lanceolate, 6 to 15 centimeters long and pointed at both ends. Flowers are white, fragrant, borne in considerable numbers in hairy terminal panicles, 6 to 10 centimeters long. Calyx segments are very small and toothed. Corolla-tube is slender, about 1.5 centimeters long, with obtuse lobes about half the length of the tube. Fruit is black when dry, rounded, about 6 millimeters in diameter.

• A shrub or small tree, 3—5 m tall, with opposite branches; young twigs glabrous, puberulent or pubescent. Leaves opposite, simple, very variable, ovate to oblong, 6—13 cm x 2—5 cm, base acute or cuneate, apex obtuse to acute, glabrous or hairy underneath; petiole 1—2 cm long; stipules interpetiolate, connate at base, distinctly cuspidate. Inflorescence a terminal, compact, erect corymb or corymbose panicle, up to 6 cm long; peduncle short; bracts large, membranaceous, cupuliform, persistent. Flowers bisexual, 4-merous, white, fragrant, protandrous, pedicel short; calyx campanulate, teeth tiny; corolla tube cylindrical, 8—12 mm long, rather thick, lobes obtuse, up to 4 mm long, contorted in bud; stamens inserted at corolla throat, with short filaments, anthers dorsifixed, sagittate and conspicuously twisted; disk annular; ovary inferior, 2-locular, 1 ovule per cell, style filiform, long-exserted, stigma 2-lobed, lobes very short. Fruit a globose drupe, 5B-6 mm in diameter, with 1—2 pyrenes, ripening black; pyrene 1-seeded, thin-walled, plano-convex, with a wide, circular excavation. Seedling with epigeal germination; cotyledons leafy, green. (PROSEA) (41)

Distribution
- From Batan Islands and northern Luzon to Mindanao, in most or all islands and provinces and often common in primary forests, at low and medium altitudes.
- Also reported from India to China and through Malaya to tropical Australia.\

Constituents
• Roots contain a green resin, starch, an organic acid, a bitter glucoside resembling salicin.
• Stems contain essential oil, resin, alkaloid, tannin and a pectic principle.
• Petroleum ether and methanol extracts have yielded glycosides, phytosterols, saponins, flavonoids and alkaloids.
• Phytochemical studies of leaves isolated linoleic acid, (9z, 12z, 15z)-octadeca- 9, 12, 15-trienoic acid, proanthocyanadin, epicatachein and fercilic acid. (9)
• Phytochemical screening of ethanolic and methanolic extracts of leaves for secondary metabolites yielded alkaloids, carbohydrates, tannins, chlorogenic acid, steroidal glycosides, steroids, and flavonoids. (16)
• GC-MS analysis of ethanolic extracts yielded 36 phytoconstituents belonging to types of acids, alkanes, amines, esters, and phenolic compounds. Based on percentage peaks, dominant compounds ranging from 59-63-60% were 1,2- benzene dicarboxylic acid, diethylester(CAS) Ethyl phthalate, 2,4- Imidazolidinedione, 1-[(5-nitro-2-furanyl) methane]amino]-(CAS)upiol, phalic acid, allyl ethyl ester (CAS) Ethylallylphthalate, 1, 3-dioxoline, tartronic acid, (P- Ethoxyphenyl) diethyl ester. (16)
• Study of leaves for volatile oil yielded 24 compounds. The major constituents were ß-pinene (25.45%), ß-eudesmol (7.06%) and tricyclene (5.74%). The yield of essential oil from aerial parts was 0.05% (v/w). (5)
• Phytochemical screening of flowers yielded alkaloids, tannins, saponins, flavonoids, glycosides, and steroids. (see study below) (26)
• Study of various root extracts and fractions yielded four compounds i.e., chlorogenic acid, fercilic acid, salicine, and oleic acid. These compounds were isolated for the first time from the roots of P. indica. (28)
• Phytochemical screening of leaves revealed: Chlorophyll a (1.21 mg/g), chlorophyll b (1.61 mg g), total chlorophyll (2.82 mg g), carotenoids (0.57 mg g), total soluble sugars (30.08 mg g), total soluble starch (13.54 mg g) total soluble proteins (47.81 mg g), total free amino acids (5.77 mg g), total phenol (7.67 mg g), hydroxyl phenols (5.74 mg g), and lipids (53.53 mg g). Alkaloids, tannins, steroids, phenolic compounds, saponins, triterpenoids, and cardiac glycosides were also present in the leaves. (see study below) (37)

Properties
• Bitter roots considered aperient.
• Analgesic, anti-inflammatory, antipyretic, diuretic.
• Studies have suggested anti-inflammatory, analgesic, antipyretic, antioxidant, diuretic, hepatoprotective, anthelmintic, anticorrosive, antibacterial, neuroprotective, wound healing, antidiabetic, antimicrobial, anticancer, anti-Alzheimer, radio-sensitization properties.

Parts utilized
Bark, roots, fruits, stems, leaves.

Uses
Edibility
• Fruits are edible, sweet when ripe. Used as condiment kept in vinegar.  (15)
• In some parts of India, flowers are reportedly eaten. (15)
Folkloric
• In the Philippines, poultice of stem bark used for soothing hemorrhoids. Crushed root bark in rice water and ginger drunk for dropsy or as diuretic. In the Philippines and India, root, root bark or stem bark used for intestinal obstructions.(32)
• Bark, pulverized or in decoction, is used for visceral obstructions.
• Leaves and roots used in poultices for boils and itches.
• Decoction of leaves used externally for hemorrhoidal pains.
• Bitter roots used for constipation.
• Roots, pulverized and mixed with ginger and rice water, used for dropsy.
• A local fomentation of leaves used for hemorrhoidal pains.
• Roots used for urinary complaints.
• Root used as anticephalagic.
• Fruits used as anthelmintic.
• Decoction of stem used as febrifuge.
• Bark decoction used for arthritis.
• In Ayurveda and Siddha medicine, leaf paste used for poulticing boils and to remove pus. Leaf decoction used externally for hemorrhoids. Root decoction used as postpartum remedy. (17)
• In India, one of the herbal medicines used in the treatment of epilepsy. (24) Whole plant used for rheumatism (•) Leaf paste used for snake bites. (29) The Chiru tribe of Manipur, India, use cooked leaves for relief of jaundice. (30) Roots used for urinary diseases and as antiurolithiatic. (31)
• Leaf decocotion drunk during first days after childbirth or when childbirth is delayed; also taken for fever. Poultice of stem bark used topically for soothing hemorrhoids. Infusion of thinly cut wood taken for treatment of rheumatism. (15)
• In Ayurveda, used for treatment of asthma: a mixture of pavatta leaf juice, ginger, and red onion juice is drunk, a teaspoon twice daily. Alternatively, pavatta juice and honey in a fresh pot exposed to the sun is used fo treat asthma. Or, the panchanga of the plant is mixed with chopped garlic, raw ginger, and boiled sesame oil, and rubbed on the chest of the patient suffering from asthma. (40)
Others
• Mulch: Leaves make a good green mulch. (15)
• Scent: Infusion of fragrant flowers used after bathing. (15)
• Rituals: In northern Thailand, used by the Hmong people in religious ceremonies to communicate with ancestral spirits.

Studies
• Anti-Inflammatory / Leaves: Study of the anti-inflammatory potential of the methanol extract of Pavetta indica leaves on several models of inflammation showed activity in the proliferative phase of the inflammatory process in an effect comparable to the standard non-steroidal anti-inflammatory drug indomethacin. (1)
• Analgesic / Leaves: Study of the ethanolic leaf extract of P indica showed significant dose-dependent inhibition of pain response induced by thermal and mechanical stimuli. Results showed promising potential use of the crude extract in the treatment of pain. (2)
• Antipyretic: Study of the methanol extract of P indica reduced the pyrexia induced by yeast, found statistically significant, and indicates a potential for the extract's use as an agent against pyrexia. (3)
• Diuretic / Leaves: Study of petroleum and ether extracts of leaves of Pavetta indica exhibited significant diuretic activity. Effect was attributed to the presence of flavonoids. Results support its use as a diuretic agent. (4)
• Essential Oil: Study yielded 24 compounds. The major constituents of the oil were ß-pinene (25.45%), ß-eudesmol (7.06%) and tricyclene (5.74%). Oxygenated monoterpenes and sesquiterpene hydrocarbons were minor components. (5)
• Hepatoprotective / CCl4 / Paracetamol / Leaves: Study of an aqueous leaf extract on CCl4-induced hepatotoxicity in rats showed hepatoprotective activity as measured by reduction in biochemical parameters and histopathological findings. (7) An ethanol extract of P. indica leaves inhibited paracetamol induced liver toxicity in albino rats at 100 mg/kg and 200 mg/kbw in measures of biochemical values (SGPT, SGOT, APO4, S albumin). (21)
• Antioxidants / Nutrients / Minerals: Study showed the leaves to be a good source of antioxidants such as ß-carotene, vitamin C and phenolics. Leaves showed to be rich in nutrients such as crude protein, carbohydrate, crude fiber, and minerals like Na, K, Ca, S, P, Fe, Mn, Cu and Zn. (8)
• Antihelmintic / Enterobium vermicularis Infestation: Treatment with P. indica decoction caused partial or complete reduction of symptoms and absence of ova of E. vermicularis. Study show decoction of P. indica can be an effective treatment for Purishaja Krimi (E. vermicularis infestation). (10)
• Antidiabetic / Leaves: Study of methanolic extract of leaves of Pavetta indica in alloxan-induced Wistar albino diabetic rats significantly reduced blood sugar. (11)
• Antimicrobial / Leaves / Flowers: Study tested aqueous and organic solvent extracts of leaves of Pavetta indica against B. subtilis, E. coli and Saccharomyces cerevisiae. Most of the leaf extracts showed activity against B. subtilis. None showed activity against E. coli and S. cerevisiae. (12) In a study of five ethnomedicinal plants, Pavetta indica showed great inhibitory activity against Staphylococcus aureus and Escherichia coli. (26) Study of an ethanol extract of flowers of Pavetta indica showed high antibacterial activity with range of inhibition between 30 ± 5.3 to 40 ± 7.1 mm. respectively. (27)
• Anticorrosive Property / Leaves: Study evaluated the anticorrosive nature of P. indica leaf extract on mild steel corrosion in HCl and HxSO4 media. Results showed the extracts could inhibit mild steel corrosion. (13)
• Anticholinesterase / Antidiabetic / Antioxidant / Neuroprotective: Study evaluated crude methanolic extracts and fractions of Acalypha alnifolia, Pavetta indica and Ochna obtusate for acetylcholnesterase, butyrylcholinesterase, and α-glucosidase inhibitory activities. Active chloroform fractions showed prominent ability to scavenge DPPH and ABTS reactive species and neuroprotective effects against H2O2 induced cell injury. The fractions showed significant anticholinesterase, antidiabetic, antioxidant, and neuroprotective effects attributable to phenolic, flavonoid, and terpenoid contents. Study suggests further studies for the potential of a multifunctional therapeutic agent as AD and DM dual therapy. (18)
• Antioxidant / Aerial Parts: Study evaluated the in vivo antioxidant and lipid peroxidation effect of different extracts of aerial parts of Pavetta indica. A methanolic extract of PI in high fat diet rats lowered the concentration of TBARS, with significant (p<0.01) increments in the levels of SOD, CAT, GPx, GR, GST, and GSH. Results suggest the ME is a significant source of natural antioxidant, which may be useful in preventing various oxidative stresses. (19)
• Anthelmintic / Leaves and Roots: Study evaluated various extracts of roots and leaves of Pavetta indica for anthelmintic activity against Indian adult earthworms Pheretima posthuma and roundworm Ascaridia gali. All the extracts showed dose-dependent activity. Root extract showed more potent activity, with the methanol extract of roots showing shortest time for paralysis and death at 100 mg/ml. (20)
• CuO, MgO and Ag2O Nanoparticles / Anti-Inflammatory / Leaves: Study reports on the biosynthesis on the novel and green synthesis of copper oxide, magnesium oxide, and silver oxide nanoparticles using a leaf extract of P. indica. The plant showed significant anti-inflammatory activity on denaturation of egg albumin. (22)
• Wound Healing / Roots: Study evaluated the wound healing activity of different extracts of leaves and roots in albino rats using excision and incision wound models. A methanolic extract ointment showed significant healing in both wound models, as evidenced by increased rate and extent of wound closures and increased tensile strength in healing wounds. The root extracts showed more potent healing compared to leaf extracts. (23)
• Anticancer / Cytotoxic Effect and Radiation Sensitization / Aerial Parts: Study of methanol extract of leaves and branches of P. indica (MEPI) for anticancer effect showed cell cycle arrest at the sub-G1 phase and induced apoptosis, evidenced by activation of caspase-8, -3, -7, and c-PARP. Western blotting showed MEPI significantly reduced the levels of markers of epithelial-mesenchyma transition, such as Vimentin, Snail, Slug, and matrix metallopeptidase 9. Co-treatment of MEPI and doxorubicin showed synergistic reduction in cell viability. MEPI also induced radiation sensitization of TNBC cells. GC-0MS revealed 5,6-dehyrdokawain (DK) as the major constituents of MEPI. DK exhibited significant anti-invasive and anti-metastatic effects. Results suggest rationale for investigating the molecular mechanisms of action of MEPI in TNBC. (34)
• Antimicrobial / Leaves: Study evaluated the antimicrobial potential and phytochemical constituents of leaves of Pavetta indica. Absolute ethanol extract showed significant antimicrobial activity against all tested pathogens (4 bacteria: E. coli, B. subtilis, S. typhi, S. pyogenes; 3 fungi: A. niger, A. candida, T. rubrum), followed by the aqueous extract, with maximum inhibition zones of 21 mm and 6 mm respectively. (see constituents above) (37)|
• Anti-Alzheimer / Leaves: Alzheimer's disease (AD) is a neurological dysfunction of the brain cause by neurodegeneration and oxidative stress. Some virus, such as Herpes viruses (HSV-1 and HSV-2) are causative agents of AD and result in ß-amyloid peptide and tau protein accumulation in the brain. Antiviral drugs like valacyclovir, acyclovir, and foscarnet, reduced ß-amyloid and P-tau. Study evaluated the effect of using P. indica methanolic leaf extract and acyclovir against AD induced by streptozotocin in wistar rats. Rivastigmine 2 mg/kg orally was used as standard. Intracereboventricular-STZ produced significant alternations in behavioral assessments and inflammatory markers and disturbed neurotrans-mitter mediators. Acyclovir and P. indica ME treatments dose-dependently abrogated the STZ-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir may be attributable to the antiviral, antioxidant, and anti-inflammatory effects. (38)
• Analgesic / Anti-Inflammatory / Safety / Leaves: Study evaluated the anti-inflammatory and analgesic effects of P. indica extract of leaves in wistar albino rats. Anti-inflammatory activity was evaluated using Carrageenan-induced paw edema and cotton pellet induced granuloma, while analgesic activity was evaluated using hot plate method. Results showed potent anti-inflammatory actions in both acute and chronic studies and significant analgesic effect suggesting central analgesic activity. The test drug was safe in high dose of 2000 mg.kg in acute toxicity testing. (39)

Availability
- Wild-crafted.
- Oil, supplements in the cybermarket.