Orthosiphon aristatus (Blume) Miq.

Last updated: 12 March 2015

Scientific Name

Orthosiphon aristatus (Blume) Miq.

Synonyms

Clerodendranthus spicatus (Thunb.) C.Y.Wu, Clerodendranthus stamineus (Benth.) Kudô, Clerodendrum spicatum Thunb., Ocimum aristatum Blume, Ocimum grandiflorum Blume [Illegitimate], Orthosiphon grandiflorus Bold. [Illegitimate], Orthosiphon spicatus (Thunb.) Backer, Bakh.f. & Steenis [Illegitimate], Orthosiphon spiralis (Lour.) Merr., Orthosiphon stamineus Benth., Orthosiphon tagawae Murata, Orthosiphon velteri Doan [Invalid], Trichostema spirale Lour. [1]

Vernacular Name

Malaysia Kumis kucing, misai kucing [2][3]
English Java tea, cat’s whiskers [2][4]
China Mao xu cao, mao xuhua [4][5]
Indonesia Remujung, kumis kucing, songkok kucing, remujung (Java); sesalaseyan, soengok kuceng (Madura) [6]
Philippines Balbas-pusa [2]
Thailand Yaa nuat maeo [2][4]
Vietnam R[aa]u m[ef]o, râu mèo , cây bông bạc [2][7]
Cambodia Kapen prey [2]
Laos Hnwad meew [2]
France The de Java, moustache de chat, barbiflore, orthosiphon [2][7].

Geographical Distributions

Orthosiphon aristatus is distributed from India, Indo-China and Thailand, through Malesia to tropical Australia [2][7][8]. However it is apparently rare in Borneo, Sulawesi and the Mollucas [2]. This plant can be found in forest edges or along the streams [7].

Botanical Description

O. aristatus is a plant from the family of Labiatae. It is a perennial herb measuring 25-200 cm in height, poorly branched, quadrangular and had an ascending stem. [2]

The leaves are oppositely decussate, the blade ovate or rhombic in shape, 2-9(-12) cm x 1.5-5 cm, cuneate at the base, acuminate at the apex, margin toothed-like, smooth or minutely pubescent, glandular-punctate. The petiole 0.5-2(-4.5) cm long and stipule is absent. [2]

The inflorescence in an opposed cyme arranged in terminal racemes and measuring 7-29 cm long. the flower prdicellate, calyx 2.5-4.5 mm and up to 12 mm in fruit, bilibiate and gland-dotted. The corolla measures about 10-20 mm long, bilibiate and tubular with a white or pale in colour. The stamens 4, extended from the corolla tube. Ovary superior, style project outside, slender and shallowly cleft stigma. [2]

The fruit will split into 4 oblong-ovoid nutlets measuring 1.5-2 mm long with a brownish colour and rugose surface. [2]

Cultivation

Uses

O. aristatus which also known as O. aristatus always cultivated as an ornamental plant in the gardens as the flower of this plant is unique and beautiful. [2]

 

44

Figure 1: Fully grown O. aristatus plants ready for first harvest

Soil Suitability and Climatic Requirement

O. aristatus can be grown and cultivated on any soil types including sandy soil like bris and tin tailings. The plant needs an average monthly rainfall of 180-200 cm to grow well. Irrigation should be provided during the dry season. O. aristatus can withstand waterlogged conditions. The growth is not affected although the crop has been waterlogged for 24 hours. [9]

Field Preparation

Land Preparation

The field is usually ploughed at least one month before planting. This will ensure that weeds and other shrubs found in the planting area can be removed. Ground Magnesium Limestone (GML) should be applied after the first ploughing to ensure the lime and the soil are thoroughly mixed. The rate of GML application depends on the soil pH. The soil pH required for optimum crop growth is 5-6. [9]

Production of Planting Materials

Stem cuttings are usually used as the source of planting materials. The cuttings start to produce roots after two weeks in the polybags. The seedlings are ready for field planting after 4-5 weeks in the nursery. For commercial planting using transplanting machines, seedlings should be raised in plastic or polystyrene trays. [9][10][11][12][13][14]

44fig2

Figure 2: Stem cuttings are raised in polybags for field planting

Field Planting

The recommended plant spacing is 150 cm between rows and 30 cm between plants within row. This spacing will produce a population density of about 22,200 plants per hectare. Planting can be done manually or using tractors. [9][15]

44fig3

Figure 3: Stem cuttings are raised in polybags for field planting

 

Field Maintenance

Fertilisation

For bris soil, the recommended rate of chicken manure application is 10 t/ha together with the inorganic fertiliser NPK Green (N:P:K=10:10:10) at 1 t/ha. These fertilisers are applied at 3 days before planting and subsequently at 6 months intervals. Half the rates of chicken manure and inorganic fertiliser are recommended for alluvial soil. [9][16]

Weed Control

Weed control is needed only at the early stages of plant growth. At the maximum growth stage, the dense canopy can control weeds naturally. Plastic mulch can also be used to control weeds. [9]

Water Management

Several irrigation systems can be used depending on the soil types and water source. For commercial planting, sprinkler, rain gun or furrow irrigation can be used. Drip irrigation is suitable when plastic mulch is used. [9]

Pest and Disease Control

There are no serious pest and disease problems affecting O. aristatus. [9]

Harvesting

The first harvest is at 10 weeks after field planting. The shoots are cut at about 30 cm from the tip. The recommended harvesting intervals is every 2 weeks. The potential yield depends on variety and crop vigour. The potential dry yield for about 20 harvests is 5-6 t/ha/year. The ratio of fresh to dry weight (drying ratio) is about 4-5. [9]

 

44fig4

Figure 4: Handling of harvested O. aristatus leaves.

 

Postharvest Handling

The dry product should be free from contaminants (weeds, sand particles etc.) and free from fungus. For this purpose, the harvested shoots should be dried as soon as possible. If necessary, the leaves are separated from the stem after drying as the leaves are brittle and easily separated from the stem. The ratio of leaf weight to stem weight is approximately 1:1. To ensure the bioactive component is not affected, the drying temperature should not exceed 45ºC. Several drying systems such as sun drying, commercial oven drying or tobacco barn drying can be used. [9]

 

44fig5

Figure 5: Drying of the O. aristatus leaves in the tobacco drying barn.

 

Estimated Cost Of Production

The production cost per hectare per year (for 20 harvests) for O. aristatus is RM 9,100 for bris soil and RM 8,100 for alluvial soil. The main component is input cost such as fertiliser, plastic mulch and irrigation equipment. The production cost for bris soil is higher due to the high cost of chicken manure and the organic-based fertiliser. The estimated production cost is RM 1.82-1.52/kg for bris soil and RM 1.62-1.35/kg for alluvial soil. The production cost was estimated based on the cost of current inputs during writing of this article. [9]

Chemical Constituent

Aqueous extract of O. aristatus leaves has been reported to contain diterpenes (e.g. neoorthosiphols A and B, orthosiphols A and B, orthosiphonones A and B), flavonoids (e.g. sinensetin, tetramethylscutellarein, 5-hydroxy-6,7,3’,4’-tetramethoxyflavone) and benzochromenes (e.g. methylripariochromene A, acetovanillochromene, orthochromene A). [17][18]

Methanol extract of O. aristatus leaves has been reported to contain flavanoids (e.g. sinensetin, eupatorin, salvigenin, scutellarein tetraramethyl ether, 5-hydroxy-6,7,3’,4’-tetramethoxyflavone, 6-hydroxy-5,7,3’-trimethoxyflavone, 5,6,7,3’-tetramethoxy-4’-hydroxy-8-C-prenylflavone, 3’-hydroxy-5,6,7,4’-tetramethoxyflavone), diterpens (e.g. orthosiphols A- E), triterpenes (e.g. ursolic acid, oleanolic acid, betulinic acid, hydroxybetulinic acid, α-amyrin, β-amyrin, maslinic acid, orthosiphonic acid) and caffeic acid derivative (e.g. rosmarinic acid). [19][20][21][22][23][24]

Methanol extract of aerial part of O. aristatus has been reported to contain diterpenes (e.g. orthosiphols F-Q, staminolactones A, staminolactones B, and norstaminol A, staminols A and staminols B, norstaminone A, nororthosiphonolide A, and orthosiphonone A), flavonoids (e.g. ladanein, 5-hydroxy-6,7,39,49-tetramethoxyflavone, tetramethylscutellarein, 6-hydroxy-5,7,49-trimethoxy-flavone, 7,39,49-tri-O-methylluteolin), steroid (e.g. β-sitosterol), vomifoliol, and aurantiamide acetate. [25][26][27][28]

Ethyl acetate extract of O. aristatus leaves has been reported to contain flavonoids (e.g. tetramethylscutellarein, eupatorin, 5-hydroxy-6, 7’,3',4’-tetramethoxyflavone, 3’-hydroxy-5,6,7,4’-tetramethoxyflavone, salvigenin, trimethylapigenin, and tetramethylluteolin). [29]

Essential oil of O. aristatus leaves has been found to contain monoterpenes  (e.g. α-pinene, ρ-cymene, 1,8-cineol, limonene, linalool, camphor, δ-terpineol, methylchavicol, borneol, menthone, isomenthone, γ-elemene, α-cubebene, damascenone, α-copaene, eugenol, methyleugenol), sesquiterpenes (e.g. β-carryophyllene, α-humulene, β-elemene, β-bourbonene, cis-caryophyllene, geranylacetone, β-ionone, germacrene D, α-muuiolene, δ-cadinene, germacrene B, dehydroionone, caryophyllene oxide, hexahydrofamesylacetone) and others (hexanal, trans-2-hexanal, cis-3-hexen-1-ol, hexan-1-ol, 4-heptenal, heptenal, benzaldehyde, camphene, 1-octen-3-ol, β-pinene, 3-octanol, 2-pentenylfurane, 2-amylfurane,  acetophenone, cis-2-octenal, phenylacetaldehyde, trans,cis-octa-3,5-dien-2-one, cis-linalooloxide, trans,trans-octa-3,5-dien-2-one,  trans-linalooloxide, undecan, 2,6,6-trimethyl-2-cyclohexe-1,4-dione, perillen,  trans-2-(cis)-6-nonadienale, decanal,  naphthalene, dodecane, citronellol, carvone, β-cyclocitral, trans-anethol, isobornylacetate, safranal, 1-methylnaphthalene, bornyl acetate, tridecan, 2-methylnaphthalene, trans,trans-deca-2,4-dienal). [30]

Plant Part Used

Leaves. [31][32]

Traditional Use

The stem and leaves of O. aristatus are best collected before the flowering period of the plant and it was found that the purple flowered variety is more potent than the white flowered variety. The plant is harvested before flowering which is either on March or April, roots removed and plant is washed and dried under the sun [31]. The dried leaves decoction is used to treat cases of strangury and dysuria [32].

The diuretic effects of leaves of this plant had been recognized in the South-east Asian community for a very long time. To this end, many had recommended it is use in the treatment of various kidney diseases from infection to renal calculi. Urinary tract infection be it bladder or higher up is treated with a decoction of fresh leaves to be taken twice a day. To treat kidney stones the traditional medical practitioners prescribe the whole plant whether fresh or dried. [32]

Its ability to excrete uric acid had been recognized in the 19th century such than one British doctor used it to treat gout. The Filipinos takes a decoction of the leaves to relieve gout [33]. Amongst the Kenyah people of Sarawak, the young twigs and leaves are made into tea for treatment of backache [34]. The decoction of leaves of O. aristatus has been prescribed in Javanese traditional medicine (jamu) for the treatment of hypertension and diabetes [18] and with addition of Carica papaya leaves, the decoction can treat joint numbness [35]. It has been proven that the herb can effectively treat various ailments especially those related to the kidney. The decoction prepared from the leaves is used as the remedy for capillary and circulatory disorders, kidney stones, diabetes, gout and rheumatism. Fresh leaves are chewed and swallowed to induce vomiting while the dried leaves are soaked in boiling water to make a good decoction to aid urinary process, allergy treatment, diabetes, bloated stomach (busung) [36]. In Myanmar, the crushed fresh O. aristatus leaves are used on the ulcers and wounds to reduce inflammation reactions [37]. The plant is also believed to have anti-allergic, antihypertensive, anti-inflammatory and diuretic properties [9][10][13][38][39].

Preclinical Data

Pharmacology

Anti-inflammatory activity

Orthosiphol A and orthosiphol B isolated from O. aristatus dried leaves inhibited the inflammation induced by tumor promoter, TPA (12-O-tetradecanoylphorbol-13-acetate), on male Jcl:ICR mice ears. [40]

Standardized methanol:water extract (50:50 v/v) of O. aristatus leaves (SEOS) (500 and 1,000 mg/kg) administered orally to edema-induced mice and rats respectively significantly (p < 0.05) reduced the hind paw edema in rats at three and five hours after carrageenan administration. The SEOS (1,000 mg/kg) significantly (p < 0.05) showed analgesic activity in mice and rats using acetic acid-induced writhing test and the formalin-induced licking test. [41]

Antimicrobial activity

Extracts of O. aristatus showed antibacterial activity (MIC = 7.8–23.4 mg/mL) against both serotypes of Streptococcus mutans. [42]

Antipyretic activity

Standardized methanol/water (50:50) extract of O. aristatus leaves (500 and 1,000 mg/kg) administered orally to Sprague Dawley rats (180-200 g) significantly reduced the yeast-induced elevation in body temperature of the rats. The LD50 of the extract was higher than 5,000 mg/kg body weight. [43]

Diuretic activity

Aqueous extract of O. aristatus leaves administered orally to adult male Sprague-Dawley rats (180-200 g) increased the urinary K+ excretion and the blood urea nitrogen (BUN), creatinine and glucose levels into normal ranges. However, this diuretic effect was lesser than furosemide and hydrochlorthiazide. [44]

A comparative study of the efficacy of the diuretic activity between young leaves and matured leaves of O. aristatus showed that the former was more effective as a diuretic with the time of onset being earlier and the duration of effect was being short. [45]

Methanol/water extract of O. aristatus leaves showed diuretic effects comparable to those of hydrochlorthiazide for both in acute and chronic administration of the extract to hyperuricaemic rats. The uric acid level began to reduce after the 6th hour in manners similar to that of allopurinol. [46]

Methoxy flavonoids isolated from methanol-water extract of O. aristatus leaves showed antagonistic effect on adenosine receptors, thus the affinity of these isolated compounds as adenosine receptor ligands allows them to be associated with diuretic activity. [47]

Hydro-alcohol extract of O. aristatus showed diuretic activity in rats which pharmacological evaluations revealed that they led to an increase in urine flow. Urinary sodium excretion was also increased. [48]

Kidney stones activity

Aqueous extract of O. aristatus leaves and those of Sonchus arvensis was found that at concentrations of 5%, 7.5% and 10% the dissolution rate calcium stones was higher in the former than those of the latter. [45]

Antihypertensive activity

Methylripariochromene A from aqueous extract of O. aristatus leaves administered subcutaneously to conscious stroke-prone spontaneously hypertensive rats decreased in systolic blood pressure. [18]

Methylripariochromene A from aqueous extract of O. aristatus leaves administered subcutaneously to conscious male SHRSP rats decreased the systolic blood pressure and heart rate in a concentration-dependent suppression of contractions induced by high K+, l-phenylephrine or prostaglandin F2alpha in endothelium-denuded rat thoracic aorta. The compound also caused a marked suppression of contractile force without a significant reduction in the beating rate in isolated bilateral guinea pig atria, and increased urinary volume and the excretion of Na+, K+ and Cl- for 3 h after oral administration with a load of saline in fasted rats.  [49]

Two migrated pimaranetype diterpenes (neoorthosiphols A and neoorthosiphols B) isolated from the extract of O. aristatus exhibited concentration-dependent suppression of contractions induced by K+ in endothelium-denuded rat thoracic aorta. [17]

Antidiabetic activity

Aqueous extract of O. aristatus leaves (0.2, 0.5, and 1.0 g/kg) administered orally to streptozotocin-induced diabetic male Wistar rats (180-450 g) reduced the plasma glucose level in a dose dependent manner in both normal and diabetic rats during glucose tolerance test. After repeated administration of the extract for another 7 to 14 days, the plasma glucose levels of the diabetic rats were found to be reduced. At the same time the lipid profile (triglycerides and the LDL cholesterol) showed significant (p < 0.05) reduction whilst the HDL cholesterol showed a significant (p < 0.05) increased. [50]

Hepatoprotective activity

Methanol/water extract of O. aristatus inhibited the free radical scavenging and lipid peroxidation activities. The rats were pre-treated with the same extracts before induced liver damage on the rats using CCl4. It showed that the extent of liver damage was reduced in a dose dependent manner and the levels of AST and ALT was decreased. [51]

Gastroprotective activity

Methanol extract of O. aristatus administered to ethanol-induced gastric ulcer rats showed antiulcerogenic activity in the model. Histologically, it showed improvement in the healing of mucosal damage in groups received the extracts. [52]

Nitric oxide inhibition activity

Compounds (2-O-deacetylorthosiphol J, siphonols A, B, C and E, orthosiphols H, staminols A) isolated from the methanol extract of O. aristatus inhibited the nitric oxide (NO) production by lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells in a dose-dependent manner. [53][54]

Highly-oxygenated isopimarane-type and staminane-type diterpenes compounds isolated from O. aristatus also showed similar effects for their inhibition activity on NO production by LPS-activated macrophage-like J774.1 cells in a dose-dependent manner. [55]

Orthosiphols A, B, D, U, and X isolated from methanol extract of O. aristatus inhibited the NO production in LPS-activated macrophage-like J774.1 cells compared to NG-monomethyl-L-arginine (L-NMMA) (positive control) in a dose-dependent manner with Orthosiphols U displayed the strongest activity (IC50 = 6.4 μM). [56]

Antiproliferative activity

Various diterpene and flavonoids isolated from O. aristatus aerial parts showed antiproliferative activities against liver metastatic colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cell lines. [25][26][27][28]

Toxicities

Acute toxicity studies of standardized extracts of O. aristatus leaves were done using Sprague Dawley (SD) rats. At a dose of 5,000 mg/kg body weight, no toxic effects were observed during the four days period of the experiment. No lethality was reported. All the parameters measured (general behaviour, BW, food and water intake, relative organ weight per 100 g BW, hematology and clinical biochemistry) were unaffected as compared to the normal rats. The acute toxicity LD50 was estimated to be > 5,000 mg/kg BW. [57]

Chronic toxicity study was carried out using the methanol/water extract of O. stamineuson young female SD rats. It was found that continuous chronic administration in the dose of 0.5 g/kg, 1 g/kg, 3 g/kg and 5 g/kg body weight for 14 days did not produce any adverse effects. There were no reports of lethality. However, it was noted that there was a significant decrease in some serum biochemical parameters, i.e. AST and ALT, and increased in liver weight after 14 days of the study. [58]

Clinical Data

Clinical findings

A clinical study was performed to compare the efficacy of an herbal plant, O. aristatus and the drug sodium potassium citrate (SPC) in treatment of renal calculi. In this study, 48 patients were divided into two groups: G1 (was given 2.5g dried O. aristatus twice daily) and G2 (was given 5-10g of granular SPC, three times daily). After treatment, 90% of the initial clinical symptoms such as back pain, fatigue, dyspepsia, abdominal pain, fever, myofascial pain, paresthesia at the frank, headaches and joint pain were relieved. Fatigue and loss of appetite were observed in 26.3% of G2 subjects. This study showed the efficacy of O. aristatus in reducing the stone size and related symptoms. [59]

Diuretic effects were observed in man, such as increased diuresis and elimination of chlorides and urea. It was reported that there are no influences recorded for 12 and 24 hours urine output or on the sodium excretion for any of drugs when tested under standardized conditions in a placebo controlled double-blind crossover model. [60]

In clinical studies with healthy volunteers in Thailand, the extract of Folia orthosiphonis was shown to cause the increase of the citrate and oxalate excretion. Although a higher level of oxalate may increase the risk of kidney stones, the increased citrate output helped prevent stone formation. [61]

Precautions

During the use of the herbal substance and preparation, appropriate fluid intake is recommended. A doctor or a qualified health care professional should be consulted if complaints of symptoms such as fever, dysuria, spasms or blood in the urine persist during the use of the medicinal herb. Utilization of this herb is not recommended in case of oedema due to limited heart and kidney function. [62]

The pharmaceutical form should be described by the European Pharmacopoeia full standard term. It is highly recommended for liquid extracts containing ethanol, the appropriate labelling for ethanol, taken from the “Guideline on excipients in the label and package leaflet of medicinal products for human use” must be included. [62]

In other cases, particularly in treating diseases of urinary system, care should be taken when consuming this Orthosiphon herb as slight increase of kidney function enzymes was recorded [44]. Product from this herb also needs to be stored below 30°C and need to be protected from light and moisture [62].

Side effects

No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages. [63]

Pregnancy/Breast Feeding

Not to be used by pregnant or nursing women without supervision of a healthcare professional. Safety during pregnancy and lactation has not been established. Due to the inadequate data, the use during pregnancy and lactation is not recommended. [62]

Age limitation

Utilization of this herb is not recommended in children and adolescents under 18 years of age due to lack of established data. [62]

Adverse reaction

A doctor or a qualified health practitioner should be consulted if adverse reactions occur. [62]

Interaction & Depletion

Interaction with drug

There is possible summation of action when taken with diuretics especially in the treatment of hypertension and congestive cardiac failure. Orthosiphon exhibited diuretic activity, but was less potent than furosemide and hydrochlorothiazide. Caution should be exercise when taking this drug in the presence of cardiac and renal insufficiency. It also can cause slight increase of kidney function enzymes. [44]

Interaction with other Herbs

No documentation.

Contraindications

Diuretics using leaves of O. stamineus is not recommended in cases of oedema due to cardiovascular and renal insufficiency especially in the presence of potassium which may cause adverse reaction especially when given together with digitoxin. [62][63]

Use of this herb for irrigation therapy is contraindicated in the presence of oedema resulting from reduced cardiac or renal activity. [20]

Utilization of herbal substance and preparation is also contraindicated in people who are hypersensitive to any of the active substances. [62]

Case Report

No documentation.

Dosage

Dosage Range

Dried O. aristatus leaves for tea preparation: 6 to 12 g daily in divided doses (for adults and elderly). [62]

Most Common Dosage

Herbal preparations of O. aristatus leaves (for adults and elderly) [62][63]:

  1. Liquid extract: 2 g in 150 mL of hot water for 15 minutes. At least 1 to 2 times daily.
  2. Dry extract (5-7:1): 360 mg, 3 to 4 times daily.
  3. Dry extract (8-12:1): 200 to 400 mg, 3 times daily.
  4. Dry extract (7-8:1): 280 mg, 3 times daily.

Standardization

Following the method of administration, for oral use, consumers need to ensure an increase of the amount of urine by controlling the adequate fluid intake which is required during treatment. [62]

Poisonous

No documentation.

Line drawing

No documentation.

References

  1. The Plant List. Orthosiphon aristatus (Blume) Miq. ver1.1 [homepage in the internet]. c2013 [updated 2012 March 23; cited 2014 Nov 13] Available from: http://www.theplantlist.org/tpl1.1/record/kew-144294
  2. Dzulkarnain B, Widowati L, Isnawati A, Thijssen HJC. Orthosiphon aristatus (Blume) Miq. In dePadua L S, Bunyapraphatsara N, Lemmens R H M J, editors. Plant resources of South-East Asia no. 12(1): medicinal and poisonous plants 1. Leiden, Netherlands: Backhuys Publisher, 1999; p. 368-371.
  3. Zhari I, Norhayati I, Jaafar L. Malaysian herbal monograph. Kuala Lumpur: Malaysian Monograph Committee, 1999; p.101.
  4. Philippines medicinal plants. Kabling-gubat. Orthosiphon aristatus (Blume) Miq. [homepage on the internet]. No date [updated 2014; cited 2014 Oct 14] Available from: http://www.stuartxchange.com/KablingGubat.html
  5. Desa N, editor. 1001 misteri alam: Menyingkap rahsia khasiat sumber alam semula jadi. Shah Alam, Selangor: Buku Prima Sdn. Bhd, 2008; p. 72.
  6. Utami P, Lentera T. Tanaman obat untuk mengatasi diabetes mellitus. Jakarta: Penerbit PT Agromedia Pustaka, 2003; p. 106.
  7. National Institute of Materia Medica Hanoi- Vietnam. Selected medicinal plants in Vietnam. Vol. II. Hanoi: Science and technology publishing house, 1999; p. 159.
  8. Priyadi H, Takao G, Rahmawati I, Supriyanto B, Nursal WI, Rahman I. Five hundred plant species in Gunung Halimun Salak National Park, West Java. Bogor Barat, Indonesia: Center for International Forestry Research, 2010; p. 113.
  9. Zaharah A. Misai kucing (Orthosiphon stamineus). In: Musa Y, Ghawas MM, Mansor P, editors.  Penanaman tumbuhan ubatan & beraroma. Serdang, Selangor: Malaysian Agriculture Research and Development Institute (MARDI), 2005; p.14-20.
  10. Herbal Medicine Research Centre, Institute for Medical Research. Compendium of medicinal plants used in Malaysia. Volume 2. Kuala Lumpur: HMRC IMR, 2002; p. 148.
  11. Mat-Salleh K, Latiff A. Tumbuhan ubatan malaysia. Bangi: Universiti kebangsaan Malaysia (UKM), 2002; p. 524.
  12. Musa Y, Azimah K, Zaharah H. Tumbuhan ubatan popular Malaysia. Selangor, Malaysia: MARDI, 2009; p. 69.
  13. Wiart C. Medicinal Plants of South East Asia. Kuala Lumpur: Pelanduk Publications, 2002; p. 264.
  14. Temumen A, Zhari I, Norhayati I. Effects of flavonoids from Orthosiphon stamineus and Malphigia coccigera on the in vitro growth of calcium oxalate crystals in human urine. In: Lam C K, editors. Trends in traditional medicine research. Pulau Pinang: Universiti Sains Malaysia (USM), 1993; p. 345-443.
  15. Zaharah A, Salbiah H. Population density of misai kucing (Orthosiphon stamineus) in bris soil. Proceedings of the Seminar on Medicinal and Aromatic Plants; 2001 July 24-25; Kuala Lumpur. Kuala Lumpur: Forest Research Institute Malaysia (FRIM); 2002.
  16. Zaharah A, Wan Zaki WM, Musa Y, Salbiah H. Kesan penggunaan baja organik terhadap tanaman misai kucing (Orthosiphon stamineus) dan hempedu bumi (Andrographis paniculata) di tanah bris. Proceedings of the Seminar on Medicinal and Aromatic Plants; 2001 July 24-25; Kuala Lumpur. Kuala Lumpur: Forest Research Institute Malaysia (FRIM); 2002.
  17. Ohashi K, Bohgaki T, Matsubara T, Shibuya H. Indonesian medicinal plants. XXIII. Chemical structures of two new migrated pimarane-type diterpenes, neoorthosiphols A and B, and suppressive effects on rat thoracic aorta of chemical constituents isolated from the leaves of Orthosiphon aristatus (Lamiaceae). Chem Pharm Bull (Tokyo). 2000;48(3):433-435.
  18. Ohashi K, Bohgaki T, Shibuya H. Antihypertensive substance in the leaves of kumis kucing (Orthosiphon aristatus) in Java Island. Yakugaku Zasshi. 2000;120(5):474-482.
  19. Hossain MA, Mizanur Rahman SM. Isolation and characterisation of flavonoids from the leaves of medicinal plant Orthosiphon stamineus. Arab J Chem. 2015;8(2):218-221.
  20. Akowuah GA, Zhari I, Norhayati I, Sadikun A, Khamsah SM. Sinensetin, eupatorin, 3′-hydroxy-5, 6, 7, 4′-tetramethoxyflavone and rosmarinic acid contents and antioxidative effect of Orthosiphon stamineus from Malaysia. Food Chem. 2004;87(4):559-566.
  21. Pietta PG, Mauri PL, Gardana C, Bruno A. High-performance liquid chromatography with diode-array ultraviolet detection of methoxylated flavones in Orthosiphon leaves. J Chromatogr A. 1991;547:439-442.
  22. Hossain MA, Ismail Z. Isolation and characterization of triterpenes from the leaves of Orthosiphon stamineus. Arab J Chem. 2010;6(13):295-298.
  23. Hossain MA, Ismail Z. A new lupene-type triterpene from the leaves of Orthosiphon stamineus. Indian J Chem. 2005;44B:436-437.
  24. Takeda Y, Matsumoto T, Terao H, et al. Orthosipol D and E, minor diterpenes from Orthosiphon stamineus. Phytochemistry. 1993;33(2):411-415.
  25. Stampoulis P, Tezuka Y, Banskota AH, Tran KQ, Saiki I, Kadota S. Staminolactones A and B and norstaminol A: three highly oxygenated staminane-type diterpenes from Orthosiphon stamineus. Org Lett. 1999;1(9):1367-1370.
  26. Tezuka Y, Stampoulis P, Banskota AH, et al. Constituents of the Vietnamese medicinal plant Orthosiphon stamineus. Chem Pharm Bull (Tokyo). 2000;48(11):1711-1719.
  27. Awale S, Tezuka Y, Banskota AH, Kouda K, Tun KM, Kadota S. Five novel highly oxygenated diterpenes of Orthosiphon stamineus from Myanmar. J Nat Prod. 2001;64(5):592-596.
  28. Awale S, Tezuka Y, Banskota AH, Kouda K, Tun KM, Kadota S. Four highly oxygenated isopimarane-type diterpenes of Orthosiphon stamineus. Planta Med. 2002;68(3):286-288.
  29. Lyckander IM, Malterud KE. Lipophilic flavonoids from Orthosiphon spicatus Prevent Oxidative Inactivation of 15-lipoxygenase. Prostaglandins Leukot Essent. Fatty Acids. 1996;54(4):239-246.
  30. Hossain MA, Ismail Z, Rahman A, Kang SC. Chemical composition and anti-properties of the essential oils and crude extracts of Orthosiphon stamineus Benth. Ind Crops Prod. 2008;27(3):328-334.
  31. Fauziah M. Tanaman obat keluarga (Revisi). Jakarta: Penebar Swadaya, 2007; p. 35.
  32. World Health Organization (WHO), Institute of Materia Medica Hanoi. Medicinal Plants in Viet Nam. Manila: World Health Organization-Regional Office for the Western Pacific/Institute of Materia Medica Hanoi, 1990; p. 271.
  33. De Padua LS, Lugod GC, Pancho JV. Handbook on Philippine medicinal plants. Vol 3. Los Banos: University of Philippines, 1987; p. 31.
  34. Chai PPK. Medicinal plants of Sarawak. Kuching: Paul Chai PKK, 2006; p. 83.
  35. Wanita M. 1001 misteri alam. Shah Alam (Malaysia): Buku Prima Sdn. Bhd., 2008; p.72–74.
  36. Ong HC. Tanaman hiasan: Khasiat makanan & ubatan. Kuala Lumpur: Utusan Publications, 2006; p. 199.
  37. Department of Traditional Medicine, Ministry of Health. Medicinal Plants of Myanmar [homepage on the internet]. No date [updated 2014 Dec; cited 2015 Jan]. Available from: http://www.moh.gov.mm/file/Medicinal%20Plants%20of%20Myanmar.pdf
  38. Mat-Salleh K, Latif A. Tumbuhan ubatan Malaysia. Selangor, Malaysia: Pusat Pengurusan Penyelidikan Universiti Kebangsaan Malaysia, 2002; p. 524.
  39. Musa Y, Azimah K, Zaharah H. Tumbuhan ubatan popular Malaysia. Serdang : MARDI, 2009; p. 69.
  40. Masuda T, Masuda K, Shiragami S, Jitoe A, Nakatani N. Orthosiphol A and B, novel diterpenoid inhibitors of TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation, from Orthosiphon stamineus. Tetrahedron.1992;48(33):6787-6792.
  41. Yam MF, Asmawi MZ, Basir R. An investigation of the anti-inflammatory and analgesic effects of Orthosiphon stamineus leaf extract. J Med Food. 2008;11(2):362-368.
  42. Chen CP, Lin CC, Namba T. Screening of Taiwanese crude drugs for antibacterial activity against Streptococcus mutans. J Ethnopharmacol. 1989;27(3):285-295.
  43. Yam MF, Ang LF, Basir R, Salman IM, Ameer OZ, Asmawi MZ. Evaluation of the anti-pyretic potential of Orthosiphon stamineus Benth standardized extract. Inflammopharmacology. 2009;17(1):50-54.
  44. Adam Y, Somchit MN, Sulaiman MR, et al. Diuretic properties of Orthosiphon stamineus Benth. J Ethnopharmacol. 2009;124(1):154-158.
  45. Dalimartha S. Atlas tumbuhan obat IndonesiaVolume 2. Jakarta: Niaga Swadaya, 1999; p.128.
  46. Arafat OM, Tham SY, Sadikun A, Zhari I, Haughton PJ, Asmawi MZ. Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats. J Ethnopharmacol. 2008;118(3):354-360.
  47. Yuliana ND, Khatib A, Link-Struensee AM, et al. Adenosine A1 receptor binding activity of methoxy flavonoids from Orthosiphon stamineus. Planta Med. 2009;75(2):132-136.
  48. Beaux D, Fleureantin J, Mortier F. Effects of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L, and Actostaphylos uva-ursi (L.) Spreng in rats. Phytoter Res. 1999;13(3):222-225.
  49. Matsubara T, Bohgaki T, Watarai M, Suzuki H, Ohashi K, Shibuya H. Antihypertensive actions of methylripariochromene A from Orthosiphon aristatus, an Indonesian traditional medicinal plant. Biol Pharm Bull. 1999;22(10):1083-1088.
  50. Sriplang K, Adisakwattana S, Rungsipipat A, Yibchok-anun S. Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. J Ethnopharmacol. 2007;109(3):510-514.
  51. Yam MF, Basir R, Asmawi MZ, Ismail Z. Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract. Am J Chin Med. 2007;35(1):115-126.
  52. Yam MF, Ang LF, Salman IM, et al. Orthosiphon stamineus leaf extract protects against ethanol-induced gastropathy in rats. J Med Food. 2009;12(5):1089-1097.
  53. Awale S, Tezuka Y, Banskota AH, Adnyana IK, Kadota S. Highly-oxygenated isopimarane-type diterpenes from Orthosiphon stamineus of Indonesia and their nitric oxide inhibitory activity. Chem Pharm Bull (Tokyo). 2003;51(3):268-275.
  54. Awale S, Tezuka Y, Banskota AH, Adnyana IK, Kadota S. Siphonols A-E: novel nitric oxide inhibitors from Orthosiphon stamineus of Indonesia. Bioorg Med Chem Lett. 2003;13(1):31-35.
  55. Awale S, Tezuka Y, Banskota AH, Kadota S. Inhibition of NO production by highly-oxygenated diterpenes of Orthosiphon stamineus and their structure-activity relationship. Biol Pharm Bull. 2003;26(4):468-473.
  56. Awale S, Tezuka Y, Banskota AH, Adnyana IK, Kadota S. Nitric oxide inhibitory isopimarane-type diterpenes from Orthosiphon stamineus of Indonesia. J Nat Prod. 2003;66(2):255-258.
  57. Abdullah NR, Ismail Z, Ismail Z. Acute toxicity of Orthosiphon stamineus Benth standardized extract in Sprague Dawley rats. Phytomedicine. 2009;16(2-3):222-226.
  58. Chin JH, Abas HH, Sabariah I. Toxicity study of Orthosiphon stamineus Benth (misai kucing) on Sprague Dawley rats. Trop Biomed. 2008;25(1):9-16.
  59. Premgamone A, Sriboonlue P, Disatapornjaroen W, Maskasem S, Sinsupan N, Apinives C. A long-term study on the efficacy of an herbal plant, O. grandiflorus, and sodium potassium citrate in renal calculi treatment. Southeast Asian J Trop Med Public Health. 2001;32(3):654-660.
  60. Doan DD, Nguyen NH, Doan HK, et al. Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedied (Zea mays, Imperata cylindrical, Plantago major and Orthosiphon stamineus). J Ethnophamacol. 1992;36(3):225-231.
  61. Nirnoy M, Muangman V. Effect of Folia orthosiphonis on urinary stone promoters and inhibitors. J Med Assoc Thai. 1991;74(6):318-321.
  62. European Medicines Agency. Community herbal monograph on Orthosiphon stamineus Benth. folium; 2010. [Updated on 2014 Nov 17; Cited on 2015 Jan 5]. Available from:  http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2010/01/WC500059238.pdf
  63. Kraft K, Hobbs C. Pocket guide to herbal medicine. Stuttgart, Germany: Thieme, 2011; p.79-81.