 Gen info
- Ajuga is a genus of about 40-50 species of annual and perennial herbaceous flowering plants in the mint family Lamiaceae.
Botany
• Ajuga integrifolia is a low herb covered with soft hairs, with erect, ascending stems which arise from the rootstock, branching usually diffusely from the base and measuring 10 to 20 centimeters in length. Leaves are oblanceolate or subspatulate, 2.5 to 10 centimeters long, and 1 to 3.5 centimeters wide; the lower ones are stalked; the upper ones are stalkless and sinuate-toothed or nearly entire. Calyx is hairy, with ovate-lanceolate teeth. Corolla is pale blue or white and hairy; the tube is rarely twice as long as the calyx; the upper lip is erect and 2-fed; the side lobes or lower lobes are oblong, and the midlobe is dilated and variable in length. Stamens protrude from the upper lip. Nutlets are ellipsoid and very small.
Distribution
- Native to the Philippines.
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Found in Benguet, Bontoc, and Cavite Provinces in Luzon, and in Mindanao.
- Mainly in ravines, and sometimes in open cultivated areas, at an altitude of 600 to 1,700 meters.
- Also native to Afghanistan, Assam, Burundi, China South-Central, East Himalaya, Eritrea, Ethiopia, India, Kenya, Maluku, Myanmar, Nepal, New Guinea, Pakistan, Rwanda, Saudi Arabia, Sudan, Sulawesi, Tanzania, Thailand, Uganda, West Himalaya, Yemen, Zaïre. (13)
 Constituents
- Leaves have yielded glycoside, tannin, ceryl alcohol, and cerotic acid.
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Plant yields phytoecdysteroids, iridoid glycosides, sterols, withanolids (bracteosin A, B, and C), neo-clerodane diterpenoids. Roots have yielded steroids, palmitic acid, and heptacos-3-en-25-one. Roots yield comparatively large amounts of potassium (159 mg/100 g) compared to leaves (139 mg/100 g) (19)
- Yields glycosides, tannin, ceryl alcohol, ß-sitosterol, γ-sitosterol, cerotic acid, palmitic acid, oleic and linoleic acid, glucose, arabinose, phenolic bitter compounds.
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Study of the whole plant yielded five compounds including a new clerodane diterpenoid designated Bracteolin-A. The other compounds were a hydroxy ajugapitin, beta-sitosterol and stigmasterol.
- A dichlormethane extract yielded both clerodin- and dihydroclerodin-type diterpenes - ajubractins A-D, along with clerodin, 3-epi-car- yoptin, ajugapitin, 14,15-dihydroclerodin, 3-epi- 14,15-dihydrocaryoptin, ivain II , and 14,15-dihydroajugapitin.
- Phytochemical screening of crude extracts obtained from dried ground roots yielded alkaloids, flavonoids, phenols, glycosides, terpenoids, tannins, saponins, and steroids. Chromatographic separation from dichlormethane/methanol (1:1) extract isolated two compounds, DB6 and DB4. (21)
- Phytochemical screening of
aqueous and 70% ethanol extracts of leaves yielded phenolic compounds, flavonoids, saponins, tannins, and steroids. (see study below) (26)
- GC-MS study of hexane, methanol, and water extracts yielded hexanedioic acid, hexadecanoic acid, nonadecadiene, hexadecen-1-ol, octadecadienoic acid, nonane, phytol, henicosanal, stearyl aldehyde, and neophytadiene. The methanol extract showed greater phenolic (196.16 mg gallic acid equivalent/gram), flavonoid (222.77 mg rutin equivalents/g) and phosphomolybdate assay for total antioxidant activity (557.62 mg AAE/g). (see study below) (28)
- HPLC analysis identified the presence of flavonoids, quercetin, myricetin, and rutin and the phenolic acids, gallic acid, chlorogenic acid, and syringic acid from the aerial parts. (see study below) (33)
Properties
- Leaves have a peculiar resinous color and bitter taste.
- Considered stimulant, diuretic, depurative, and aperient.
- Plant considered aromatic, astringent, and tonic.
- Studies have suggested diuretic, anti-plasmodial, lipoxygenase enzyme inhibitory, cardiotonic, antifeedant, anti-malarial, antiarthritic, anti-dengue, antidiarrheral, antidiabetic, anti-inflammatory, antibacterial, antioxidant, anticonvulsant, antihypertensive, anti-shigellosis, anti-breast cancer, analgesic, antipyretic properties.
 Uses
Folkloric
- Unknown medicinally in the Philippines.
- Elsewhere, given for rheumatism, gout, palsy and amenorrhea.
- Used to kill lice.
- Juice of leaves used as blood purifier.
- Powdered leaves used for burns and boils.
- Juice roots used for diarrhea and dysentery.
- A bitter astringent, substituted for Cinchona in the treatment of fevers.
- Considered depurative, and an aromatic tonic especially useful in ague.
- Leaves used for fevers as a substitute for quinine.
- In Ayurveda, used in treatment of rheumatism, gout, palsy, and amenorrhea. (11)
- In Pakistan, plant decoction used for fever, kidney pain, and as cooling agent. Plant also used as stimulant, diuretic and aperient. Smoke from burning plant is considered an insect repellent. (12)
- Extracts used for swollen wounds, insect bites, eye problems, bladder afflictions, and also tumors.
- In Ethiopia, whole plant water filtrate is drunk for diarrhea and jaundice. (15) Sidama people use leaves for gastritis. (16) The Oromo people of southwest Ethiopia use pounded leaves mixed with nut oil as oral treatment for epilepsy. (22) Used for the treatment of diabetes. (26)
- In Kenya, cold infusion of leaves used for diarrhea and malaria; used for gastrointestinal afflictions associated with HIV. (17)
- In Yemen, flowers and leaves used as antiseptic and for teeth pains.
- In India, root extract used as antidote for snake bites. (24)
Others
- Perfumery: Plant is a new source of linalyl acetate, a valuable perfumery compound.
- Veterinary: Leaves given for endoparasites. (27)
Studies
• Diuretic / Leaves: Aqueous extract of leaves showed diuretic activity on rats. An alkaloidal fraction isolated from the leaves showed stimulant action on isolated perfused frog heart, rabbit auricle and rat ventricle.
• Anti-Inflammatory: Study showed the 70% ethanol extract of Ajuga bracteosa possesses promising anti-inflammatory activity, probably mediated through inhibition of COX-1 and COX-2 enzymes. Results support its traditional used for inflammatory diseases. (1)
• Antiplasmodial: Study to evaluate the antiplasmodial activity of an ethanolic extract of A bracteosa in Plasmodium berghei infected mice demonstrated a dose-dependent inhibition of parasitemia and survival time during early and in established infections. (2)
• Chemical Constituents / Enzyme Inhibition: Phytochemical study yielded Bractin A and bractin B, new sphingolipids, bractic acid, and a long-chain polyhydroxyl acid from the whole plant along with four known diterpenoids 4-7. Various activities displayed were inhibition of enzyme lipoxygenase, concentration-dependent inhibition of cholinesterase enzymes. (3)
• New Phthalic Acid Ester / Perfumery Source: Study yielded a new phthalic ester from the hexane extract of AB. Linalyl acetate was common in two oil fractions. The plant is a new source of linalyl acetate, a valuable perfumery compound. (4)
• Anti-Feedant Activity / neo-Clerodane Diterpenoids: Study yielded different neo-clerodane diterpenoids from a dichlormethane extract. Antifeedant activity against Spodoptera littoralis larvae was evaluated for the compounds obtained. (8)
• Antimicrobial Activity: Ethanolic extract of leaves showed a dose-dependent chemosuppression during early and in established infections, along with significant repository activity.
• Cardiotonic: Alkaloidal fraction showed cardiostimulant action on frog heart and rat ventricle. The activity was antagonized by dichlorisoprenaline, and may be due to liberation of catecholamine stores in the heart. (5)
• Antiarthritic: Study evaluated a 70% ethanolic extract against turpentine oil- and formaldehyde-induced acute non immunological and complete Freund's adjuvant-induced chronic immunological arthritis in albino rats. Results showed significant and promising antiarthritic activity and supports traditional use for rheumatism and other inflammatory diseases. (10)
• Anti-Inflammatory: Study evaluated the in vivo and in vitro anti-inflammatory activity of a methanolic extract of whole plant in a carrageenan-induced rat paw edema, egg albumin induced inflammation in rats. Extract doses of 500 and 750 mg/kg showed potent action compared with standard drug diclofenac sodium. (11)
• Survey / Plants Used to Treat Malaria in Ethiopia: Survey documented 42 antimalarial plants belonging to 27 families used by Sidama people of Boricha District, South Region of Ethiopia, calculating RFC (relative frequency of citation) and preference ranking. Leaf was the dominant (59.0%) part of the plant used in preparation and oral (97.4%) was the major route of administration. Ajuga integrifolia scored the highest RFC value (0.80). (14)
• Antimalarial: Study evaluated in vivo activity of crude water extracts of Ajuga remota Benth against Plasmodium berghei in mice. A wet leaf extract was most effective with 90.4% suppression of parasitemia. Extracts of air-dried and powdered flowers were least effective with 17.2% suppression of parasitemia. (20)
• Antidiarrheal
/ Aerial Parts: Study evaluated the antidiarrheal activity of 80% methanol extract of aerial part of Ajuga remota in a castor oil diarrheal model in mice. Results showed dose-dependent and significant inhibition in both frequency and onset of diarrhea. The extract also inhibited the intestinal transit of charcoal meal in a dose dependent manner in both normal and castor oil induced intestinal transit. Results suggest the presence of pharmacologically activity substances with significant antimotility and antisecretory effects. (23)
• Inhibitory Against Dengue Virus Serotype-2: Study the inhibitory effects of five different fractions (extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa and Ziziphus mauritiana, as well as their constituents (gallic acid, emodin, and isovanillic acid) against dengue virus serotype 2 (DENV-2). All the samples except for isovanillic acid exhibited significant prophylactic effects against DENV-2 infectivity (without cytotoxicity) when administered to cells before infection, but were not effective when give 6 hours post-infection. (25)
• Antidiabetic / Non-Toxicity / Leaves: Study evaluated aqueous and 70% ethanol extracts of leaves of Ajuga remota on alloxan induced diabetic mice. The LD50 of both extracts were higher than 5000 mg/kg. At doses of 300 mg/kbw and 500 mg/kbw the aqueous extracts reduced blood glucose levels by 27.83 ± 2.96% and 38.98 ± 0.67% (p<0.001), respectively, while the ethanol extracts caused 27.94 ± 1.92% and 28.26 ± 1.82%, respectively. By comparison, glibenclamide (10 mg/kbw) reduced blood glucose level by 51.06% (p<0/05). (see constituents above) (26)
• Antibacterial / Antioxidant / Anti-Inflammatory / Leaves: Study evaluated the composition, antioxidant, anti-inflammatory and antibacterial properties of methanol, hexane, and water extracts of A. integrifolia. The methanol extract showed highest scavenging activity with minimum IC50 in DPPH assay. The methanol extract showed maximum anti-denaturation activity of 3.75%. On antibacterial testing, the methanol extract showed best ZOI and MIC against methicillin-resistant Staphylococcus aureus and ß-lactam-resistant Escherichia coli. (see constituents above) (28)
• Anticonvulsant / Leaves: Study evaluated the anti-convulsant activity of A. integrifolia extract in both acute (penthylenetetrazol [PTZ] 80 mg/kg and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. Sodium valproate and phenytoin were used as positive controls for PTZ and MES models, respectively. Parameters included onset of clonus and duration of hindlimb tonic extension. The ethyl acetate extract showed superior effect among all solvent extracts in both PTZ and MES models. It significantly reduced (p<0.001) mean duration of hindlimb extension in MES. Results showed anti-convulsant activity in both acute and chronic models of seizure, and suggest potential for development of anti-epileptic drug for pharmacoresistant epilepsy. (29)
• Antihypertensive / In silico Molecular Docking Approach / Aeral Parts: Ajuga integrifolia is used as decoction to treat hypertension and diabetes. Study evaluated the scientific basis for therapeutic used of Ai as antihypertensive agent. HPLC analysis identified quercetin, myricetin, and rutin. Reptoside and 8-O-acetylharpgide were isolated from aerial parts. Biologic activity by PASS test showed flavonoids with more probability of activity than the iridoid glycosides. Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirmed the traditional use of aerial part. Flavonoids rutin, myricetin, quercetin, and kaempferol take the leading role in its antihypertensive activity. (30)
• Antidiabetic / Roots: Traditional healers have used roots for the treatment of diabetes. Study evaluated the hypoglycemic and antidiabetic activity of Ai roots on streptozotocin-induced diabetic mice. The hydromethanolic crude extract and aqueous fraction showed considerable blood glucose lowering activity at all doses (100, 200, and 400 mg/kg). Results showed significant antidiabetic activity, which supports its traditional use for treatment of diabetes mellitus. (31)
• Anti-Inflammatory / COX and Lipoxygenase Inhibitory / Leaves: Study evaluated the anti-inflammatory properties of A. integrifolia and assessed its ability to inhibit production of pro-inflammatory enzymes, cyclooxygenases (COX-1, COX-2) and lipoxygenase (5-LOX) in vitro. The extracts exhibited dose-dependent inhibition of the enzymes, with some IC50s comparable to standard anti-inflammatory drugs. The ethanol extract exhibited significant inhibition of 5-LOX (52/00 µg/ml) compared to standard zileuton (32.41 µg/mL), while COX-1 (66.00 µg/mL) and COX-2 (71.62 µg/mL) were comparable to standard indomethacin at 40.57 and 54.39 µg/mL, respectively. (32)
• Anti-Shigellosis Activity / Flavonoids and Phenolic Acids / Aerial Parts: Study evaluated the flavonoid s and phenolic contents of A. integrifolia aerial parts and its anti-shigellosis and anti-diarrheal properties. Antibacterial activity against Shigella spp. was tested using agar well diffusion method. HPLC analysis identified the presence of flavonoids, quercetin, myricetin, and rutin and the phenolic acids, gallic acid, chlorogenic acid, and syringic acid from the aerial parts. Aerial parts showed considerable activity against Shigella spp. The antioxidant activity, total phenol content, and total flavonoid content of the aerial part are in line with the anti-shigellosis activity. The five components most likely responsible for therapeutic purposes and anti-shigellosis activity are chlorogenic acid, rutin, dihydroquercetin, dihydromyricetin, and kaempferol. (33)
• Effect of Salicylic Acid and Gibberellic Acid on Biomass, Antioxidant, and Anti-Inflammatory Metabolites Production: Study evaluated the exogenous role of plant signaling molecules such as salicylic acid (SA) and gibberellic acid (GA). In vitro derived multiple shoot cultures of A. integrifolia were exposed to SA and GA. Gibberellic acid significantly raised biomass accumulation. Optimum phenolic and flavonoid contents were produced by salicylic acid treatment. A positive correlation was observed in invitro antioxidant, anti-inflammatory activities, and phytochemical production. (34)
• Anti-Breast Cancer / Dehydrocostus Lactone / Root: Study quantitatively determined dehydro-
costus lactone (DHCL)
from the root of A. integrifolia and its in silico study for anti-breast cancer activity. Estrogen receptor alpha (ERα) protein (PDB ID: 3ERT) was selected for its involvement in cell proliferation within the breast cancer cell. From molecular docking study, DHCL was found to be a promising inhibitor for estrogen receptor interaction in the breast cell and can be selected for invivo research for an anti-breast cancer drug. (35)
• Analgesic / Antipyretic / Leaves: Study evaluated the analgesic and antipyretic activities of 70% ethanol extract of A. integrifolia (EEAI) leaf in mice. Eddy's hot plate technique was used to evaluate for central analgesic activity, white acetic acid-induced writhing test was used to measure peripheral analgesic activity. Doses of 100, 200, and 400 mg/kg were administered orally. The EEAI exhibited significant analgesic effect in a dose dependent manner using hot plate method. The extract showed ability to reduce acetic acid-induced writhing in mice at all tested doses. Effects were likely due to presence of compounds such as phenols, flavonoids, tannins, saponins, alkaloids, and terpernoids, which may inhibit prostaglandin release pathways. Results suggest potential for development of effective and safe analgesic and antipyretic medications. (36)
Availability
Wild-crafted.
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