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Family Rutaceae
Buriñgit
Clausena excavata Burm. f .
PINK LIME BERRY

Jia juang pi

Scientific names Common names
Amyris graveolens Buch.-Ham. ex Steud. Buriñgit (Tagb.)
Amyris punctata Roxb. ex Colebr. Clausena (Engl.)
Amyris punctata Roxb. Pink lime-berry (Engll.)
Amyris sumatrana Roxb.  
Clausena excavata Burm. f .  
Clausena javanensis Raeusch. ex DC.  
Clausena javanensis J.F.Gmel.  
Clausena lanulata Hayata  
Clausena moningerae Merr.  
Clausena punctata (Roxb.) Wight & Arn. ex Steud.  
Clausena punctata (Roxb.) Wight & Arn.  
Clausena sumatrana (Roxb.) Wight & Arn. ex Steud.  
Clausena tetramera Hayata  
Cookia anisodora Blanco  
Cookia anisum-olens Blanco  
Cookia graveolens Wight & Arn.  
Cookia punctata Retz.  
Gallesioa graveolens M.Roem.  
Lawsonia falcata Lour.  
Clausena excavata Burm.f. is an accepted name The Plant List

Other vernacular names
BURMESE: Seitnan.
CAMBODIAN: Santhrok damney.
CHINESE: Jia huang pi, Ye huang pi, Jia juang pi.
JAPANESE: Kurausena ekisukyabata, Kurausena ekisukavata, Kurauzena ekisukyabata.
MALAY: Chemama, Daun sicerek, Cherek hitam, Kemantu hitam, Semeru, Seserek.
THAI: Chamat, Hatsa khun, Hatsa khun khok, Khi phueng, Ma lui, Mi, Mo noi, Mui yai, Oi chang, Phia fan, Rui, Saen so, Sam rui, Sam sok, Sam suea, Samat bai yai, San sok, Si som, Ya sap hin, Yom.

Etymology
Clausena excavatus derives from the Latin: Clausena, commemorating the botanist Clausen, and excavatus, to make hollow, referring to the bases of the filaments (stalks of stamens). (21)

Botany
Buriñgit is a shrub or small tree up to 15 meters high, covered with soft hairs all over. Leaves are 15 to 30 centimeters long, fetid when crushed, with 15 to 30 leaflets, alternate and short-stalked, 5 to 9 centimeters long. Flowers are 4-parted, shortly stalked, and white, borne on pyramidal panicles 10 to 30 centimeters in length. Fruit is smooth and broadly oblong, 1 to 2 centimeters long, ripening green then white or pinkish, occurring in hanging shoots. Each fruit contain 1-2 green seeds.

Distribution
- In thickets and old clearing at low altitudes in Mindoro, Culion, Palawan, and the Sulu Archipelgo.
- Also occurs in India to Indo-China and Malaya.

Constituents
- Study of leaves isolated 10 new furanone-coumarins - clauslactones A-J. together with known carbazole, clauszoline M, and a coumarin, umbelliferone.
- Study of an acetone extract of root bark yielded 10 new carbazole alkaloids, clausine M-V and clausenatine-A, together with 39 known compounds.
(12)
- Study of air-dried roots yielded six coumarins and twelve alkaloids:
binorponcitrin (1), xanthoxyletin (2), dentatin (3), nordentatin (4), clausenidin (5), scopoletin (6), dictamine (7), clausine D (8), clausine F (9), murrayafoline A (10), murrayanine (11), clauszoline I (12), 2-hydroxy-3-formyl-7-methoxycarbazole (13, 3-formyl-2,7-dimethoxycarbazole (14), clauszoline J (15), clausine H (16), murrayacine (17) and heptaphylline (18). (See study below) (19)

Properties
- Scent of resin and lime is emitted when leaves are crushed.
- Studies have shown immunomodulatory, anti-cancer, anti-viral, antinociceptive, mosquitocidal, fungicidal properties.


Parts used
Bark, roots, leaves.

Uses

Culinary
- Leaves are edible.
- Tamils reported to use it as a potherb.
Folkloric
- For bowel problems, especially coli, the Malays drink a decoction of roots.
- Pounded root used as poultice for sores, including ulcerations of the nose.
- Poultice of leaves of pounded leaves applied to the head for headaches.
- In Kelantan, roots used for yaws.
- Ulcerations of the nose treated by fumigation from burning leaves and bark.
- Decoction of flowers and leaves used for colic.
- Decoction of roots used for abdominal colic.
- Decoction of leaves given after childbirth.
- In Indonesia, leaves used for fever and to expel worms.
- In India, used to promote urination and relieve flatulence.
- In Java, plant juice used for coughs; also, as vermifuge.
- Malays used it for treatment of abdominal pain, snakebites, and for detoxification. (14)
- In Vietnam, used to promote menstruation.
- In Orissa, India, paste of roots used for body pain; decoction of roots taken for dysentery. Roots ground together with leaves of Vitex negundo, roots of Kaempferia rotunda and boiled in Pongamia pinnata oil is applied externaly for rheumatism. (
28)

Studies
Immunomodulatory:
Study investigated the in vitro immunomodulatory activities of various extracts and the Thai folklore extract of C. excavata on mouse immune system. An aqueous extract exhibited maximum effect of both respiratory burst response and lysosomal enzyme activity indicating effective phagocytic activation. The Thai folklore extract exhibited maximum activity on splenocyte proliferation assay suggesting specificity towards B-cell proliferation through T cell independent pathway. (1) Study evaluated the immunomodulating effects in Balb/C mice of aqueous extract and Thai folklore preparation of C. excavata. Results showed the CEHW gave cell mediated immunity (CMI response more than the CEHF. Results suggest potential in vivo immunomodulating activities supporting previous in vitro studies. (25)
Clauslactones / Inhibitory Effects for Tumor-Promotion: Study isolated 10 new furanone-coumarins named clauslactones A-J, together with known carbazole, clauszoline M and the coumarin, umbelliferone. The furanone-coumarins were founds to exhibit inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raju cells.
Antiproliferative / Anti-Cancer: Study investigated clausine B, a carbazole alkaloid isolated from the stem bark of Clausenas excavata for antiproliferative activities against human cancer cell lines. Results showed activity against non-hormone-dependent breast cancer, cervical cancer, ovarian cancer and hepatic cancer. The activity was attributed possibly to the phenolic group in clausine-B. (2)
Mosquito Larvicidal: Study investigated the mosquito larvicidal activities of leaf and twig essential oils from CE and its constituents against Aedes aegypti and Aedes albopictus larvae. Larvicidal assays showed the effective constituents in leaf and twig essential oils were limonene, γ-terpinene, terpinolene, β-myrcene, 3-carene and p-cymene. Among them, limonene showed the best larvicidal activity with LC50 of 19.4 µg mL-1 and 15.0 µg mL-1 against Ae aegypti and Ae. albopictus, respectively. Results suggested the essential oils may be explored as a potential natural larvicide. (3)
Antiviral / Anti-HSV2: Study evaluated 35 extracts from the leaves of five plants, including C excavata, for antiviral activity against HSV-2 strains and HSV-2 isolates. Results showed 20 extracts from the 5 plants inhibited plaque formation by HSV-2 by inactivation activity. (4)
Antinociceptive: Study of ethanolic extract of C excavata leaves showed significant antinociceptive activity on acetic acid-induced writhing in mice. (5)
Coumarin / Inhibitory Effects for Tumor-Promotion: Study of leaves yielded furanone-coumarins found to exhibit inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells. (7)
Flavonoids / Essential Oil: Study evaluated the major flavonoid compounds and predominant essential oils in C. excavata and its antioxidant, antibacterial and anticancer activities. Methanolic extract of leaves was high in phenolic content, rutin and naringin. Terpinolene was the main component in the leaf oil. There was weak DPPH scavenging activity. Antioxidant activity of flavonoids was associated with anticancer properties. Fruit oil showed better cytotoxic activity against MCF-7 cells and showed potential as a good source for breast cancer treatment. (8)
Fungicidal: Root extracts of C. excavata showed significant inhibition of pathogenic plant fungi C. gloeosporioides growth. Results suggest CE should be investigated further as potential biologic control for C. gleoesporioides. (9)
Anti- HBV / Cytotoxicity against MDR Cancer Cells: Study yielded four natural pyranocoumarins - (1) clausenidin, (2) nordentatin, (3) clausarin and (4) xanthoxyletin. Compounds 1 and 2 suppressed HBV surface antigen in HepA2 cells; 1 and 3 showed cytotoxicity against four human cancer cell lines. Others compounds showed significant activity against multi-drug resistant cancer cell lines. (10)
Anti-HIV-1 / Limonoid:
Study isolated a limonoid, clausenolide-1-ethyl ether and two coumarins, dentatin and nor-dentatin. Limonoid 1 from the crude ethanol extract of rhizomes and roots exhibited HIV-1 inhibitory activity. (11)
Cytotoxic Carbazole:
An ethyl acetate extract of the stem bark isolated a new carbazole alkaloid, clausine-TY, together with two known carbazole alkaloids, clausine-H and clausine-B. Clausine-TY showed significant cytotoxicity against CEM-SS cell line. (13)
Toxicity Study: Study in rats evaluated the safety of a methanol extract of stems. In a repeated dose 200 mg/kg/day 90-day toxicity study, no signs of toxicity and death were observed at levels of 200 mg/kg/day. Results suggest LD50 is greater than 5 g/kg. (16)
Antioxidative / Cytotoxic: Study showed a methanol extract to exhibit the most potent antioxidant activity in the DPPH and ß-carotene bleaching assays. The methanol extract inhibited 50% of cervical (HeLa) cancer cell proliferation. Results suggest the antioxidative properties of C. excavata may be one of the mechanisms of its cytotoxic properties against cancer cells. (17)
Dentatin / Prostate Cancer Cells Apoptosis: Study investigated the antiproliferative potential of dentatin, a natural coumarin isolated from C. excavata. Results showed dose-dependent inhibition of cell growth of prostatic cancer cell lines, with less cytotoxic effects on normal prostate epithelial cell line. The inhibitory effect was due to induction of apoptosis. (18)
Roots / Coumarins and Alkaloids / Cytotoxicity: Study of roots yielded six coumarins and twelve alkaloids. Compounds 4, 11, and 18 exhibited highest cytotoxicity against KB (oral cavity cancer), MCF7 (breast cancer), and NCI-H187 ( small cell lung cancer). (see constituents above) (19)

Analgesic / Anti-Platelet Aggregation:
Clausine D and F, 2,4-prenylcarbazole alkaloids from stem bark, were shown to significantly inhibit platelet aggregation. (Wu TS et al, 1992). Ethanolic extract of leaves showed analgesic activity by protecting mice from acetic acid induced writhing (Rahman MT et al, 2002). (
22)
Anti-HIV Activity:
Study isolated three carbazole derivatives, O-methylmukonal (1), 3-formyl-2,7-dimethoxycarbazole (2) and clauszoline J (3), and a pyranocoumarin, clausenidin (4), from the rhizomes and roots of C. excavata. Compounds 1-4 displayed anti-HIV activity in a syncitial assay with EC50 of 12, 29.2, 34.2, and 5.3 microm, respectively. (23)
Dentatin / Anti-Breast Cancer:
Study evaluated the effect of DTN (dentatin) on LA-7 celll-induced rat mammary tumor as confirmation of occurrence of apoptosis. Results showed significant reduction in tumor volume in the DTN-treated group, with significantly higher (p<0.05) number of apoptotic cellls. In vivo study suggests DTN inhibits proliferation, induces mitrochondria-regulated apoptosis, and minimizes LA-7 induced carcinogenesis in rat mammary glands. Results suggest a potential in breast cancer treatment. (24)
Antifungal / Leaves:
Study evaluated the antimicrobial and antifungal activity of various extracts of E. excavata. A methanolic leaf extract showed significant antifungal activity against T. rubrum and T. mentagrophytes with MIC of 62.5 µg/ml and 31.2 µg/ml. The antidermatophytic activity might be due to the flavonoid nature of some of the constituents. (26)
Gastroprotective / Ant-Ulcer:
Study evaluated the gastroprotective effect of methanolic extract of C. excavata leaves in Sprague Dawley rat ethanol-induced gastric ulcer model. Results showed gastroprotective effect of the methanol extract achieved through inhibition of gastric juice secretion and ulcer lesion development, stimulation of mucus secretion, elevation of gastric pH, reduction of ROS production, inhibition of apoptosis in the gastric mucosa, and modulation of inflammatory cytokines. (27)

Availability
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Last Updated August 2016

IMAGE SOURCE: / Clausena excavata / Mingiweng / ©All Rights Reserved/ tice (i.e. © www.NatureLoveYou.sg) / flickr / Click on graphic to see original image
IMAGE SOURCE: Photos (2) / Clausena excavata / Copyrught / © www.NatureLoveYou.sg) / click on image to go to the source page / NatureLoveYou

Additional Sources and Suggested Readings
(1)
Immunomodulatory activities of Clausena excavata Burm. f. wood extracts / A Manosroi, A Saraphanchotiwitthaya and J Manosroi
/ Journal of Ethnopharmacology, Volume 89, Issue 1, November 2003, Pages 155-160 / doi:10.1016/S0378-8741(03)00278-2
(2)
Antiproliferative Properties of Clausine-B against Cancer Cell Lines / Wan Nor I’zzah Wan Mohd Zain, Asmah Rahmat, Fauziah Othman, Taufiq Yun Hin Yap / Malaysian Journal of Medical Sciences, Vol. 16, No. 3, Pg 31-36, July - September 2009
(3)
Insecticidal activities of leaf and twig essential oils from Clausena excavata against Aedes aegypti and Aedes albopictus larvae / Sen-Sung Cheng, Hui-Ting Chang, Chun-Ya Lin et al / Pest Management Science, Volume 65, Issue 3, pages 339–343, March 2009 / DOI: 10.1002/ps.1693
(4)
Antiviral activity against herpes simplex virus type 2 of extracts from Cerbera odollam Gaertn., Clausena excavata Burm.F., Coleus amboinicus Lour., Phyla nodiflora (L.) Greene. and Thevetia peruviana Schum / Thesis / Vimolmas Lipipun, Thitima Pengsuparp, Chulalongkorn University. Graduate School / (1998)
(5)
Antinociceptive activity of Clausena excavata leaves / M T Rahman, M Alimuzzaman et al / Fitoterapia
Volume 73, Issues 7-8, December 2002, Pages 701-703 / doi:10.1016/S0367-326X(02)00211-3
(6)
Sorting Clausena names / MULTILINGUAL MULTISCRIPT PLANT NAME DATABASE
(7)
Chemical Constituents of Clausena excavata:  Isolation and Structure Elucidation of Novel Furanone-Coumarins with Inhibitory Effects for Tumor-Promotion / Chihiro Ito, Masataka Itogawa et al / J. Nat. Prod., 2000, 63 (9), pp 1218–1224 / DOI: 10.1021/np990619i

(8)
Analysis of Flavonoids and Essential Oils from Clausena Excavata and Their Medicinal Properties / Lim, Lay Sean (2004) / Masters thesis, Universiti Putra
(9)
Fungicidal properties of Clausena excavata aqueous extracts / Bryan Brunner, G Serrano Rodriguez et al /
(10)
Clausena excavata exhibits anti-Hepatitis B virus activity and cytotoxicity against multi-drug resistant cancer cells / Chung-Ren Su, Sheau Farn Yeh, Chih Miem Liu et al / Bioorg Med Chem. 2009 Aug 15;17(16):6137-43. Epub 2008 Dec 13. PMID: 19635670
(11)
Anti-HIV-1 limonoid: first isolation from Clausena excavata / Arunrat Sunthitikawinsakul, Ngampong Kongkathip, Boonsong Kongkathip et al / Phytother Res. 2003 Nov ;17 (9):1101-3 14595596 Cit:8
(12)
Alkaloidal and other constituents from the root bark of Clausena excavata / Tian-Shung Wu, Shiow-Chyn Huang et al / Phytochemistry, Vol 52, No 3, Oct 1999, Pp 523-527 / doi:10.1016/S0031-9422(99)00220-4
(13)
A New Cytotoxic Carbazole Alkaloid from Clausena excavata
/ Y H Taufiq-Yap, T H Peh,G C L Ee et al / Natural Product Research, Vol 21, No 9, 2007 / DOI:10.1080/14786410701258875
(14)
Clausena excavata Burm. f. (Rutaceae): A review of its traditional uses, pharmacological and phytochemical properties / Ismail Adam Arbab*, Ahmad Bustamam Abdul, Mohamed Aspollah, Rasedee Abdullah, Siddig Ibrahim Abdelwahab, Syam Mohan and A. H. A. Abdelmageed / Journal of Medicinal Plants Research Vol. 5(33), pp. 7177-7184, 31 December, 2011 / DOI: 10.5897/JMPR11.013
(15)
Sorting Clausea names / Maintained by: Michel H. Porcher / MULTILINGUAL MULTISCRIPT PLANT NAME DATABASE / A Work in Progress. School of Agriculture and Food Systems. Faculty of Land & Food Resources. The University of Melbourne. Australia / Copyright © 1997 - 2000 The University of Melbourne.
(16)
Acute and Repeated Dose 90-Day Oral Toxicity Studies of Clausena excavata Extract in Rats / Kunanusorn Puongtip, Panthong Ampai, Nuntasaen Narong, Pittayanurak Prapadsorn, Reutrakul Vichai / JPBMS, 2011, 12 (14)
(17)
Antioxidative and Cytotoxic Properties of the Leaf Extracts and Oil of Clausena Excavata
/ Wan-Nor I'zzah W M Z, Asmah R, Fauziah OI and Taufiq-Yap Y H / Medicinal and Aromatic Plants Seminar, 2008, Kuala Lumpur
(18)
Dentatin Induces Apoptosis in Prostate Cancer Cells via Bcl-2, Bcl-xL, Survivin Downregulation, Caspase-9, -3/7 Activation, and NF-κB Inhibition / Ismail Adam Arbab, Chung Yeng Looi, Ahmad Bustamam Abdul, Foo Kit Cheah, Won Fen Wong, Mohd Aspollah Sukari, Rasedee Abdullah, Syam Mohan, Suvitha Syam, Aditya Arya, Manal Mohamed Elhassan Taha, Bushra Muharram, Mohd Rais Mustafa, and Siddig Ibrahim Abdelwahab / Evidence-Based Complementary and Alternative Medicine, Volume 2012 (2012) /
http://dx.doi.org/10.1155/2012/856029
(19)
Chemical Constituents from the Roots of Clausena excavata and Their Cytotoxicity
/ Tawanun Sripisut, Sarot Cheenpracha, Thunwadee Ritthiwigrom, Uma Prawat and Surat Laphookhieo* / Rec. Nat. Prod. 6:4 (2012) 386-389
(20)
Clausena excavata / Synonyms / The Plant List
(21)
Clausena excavata / NP:Flora & Fauna Web
(22)
Medicinal Plants of the Asia-Pacific: Drugs for the Future? / Christophe Wiart / World Scientific
(23)
Anti-HIV-1 constituents from Clausena excavata: Part II. Carbazoles and a pyranocoumarin. / Boonsong Kongkathip, Ngampong Kongkathip, Arunrat Sunthitikawinsakul, Chanita Napaswat, Chalobon Yoosook / Phytother Res. 2005 Aug;19(8):728-31. PMID: 16177980
(24)
Dentatin from Clausena excavata induces apoptosis and reduces the tumors size of La-7 induced mammary carcinogenesis in Sprague Dawley rats / Ismail Adam Arbab, Norrakiah Abdullah Sani, Mohamed Yousif Ibrahim, Bdria Abdalla Hassan, Siddig Ibrahim Abdelwahab / International Journal of Advanced Multidisciplinary Research 2(1): (2015): 67–73
(25)
In vivo immunomodulating activity of wood extracts from Clausena excavata Burm. f. / Manosroi A , Saraphanchotiwitthaya A , Manosroi J / Journal of Ethnopharmacology 2005, 102(1):5-9 / DOI: 10.1016/j.jep.2005.04.033
(26)
RP-HPLC ANALYSIS AND ANTIMICROBIAL SCREENING OF CLAUSENA EXCAVATA BURM. F. (RUTACEAE) / C Guntupalli*, M Ramaiah, GS Kumar / Inter. J. of Phytotherapy / Vol 3 / Issue 2 / 2013 / 91-97.
(27)
Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers / Albaayit SFA, Abba Y, Abdullah R, Abdullah N / Drug Design, Development and Therapy, Volume 10, June 2016, Pages 1973—1986 / DOI https://dx.doi.org/10.2147/DDDT.S103993
(28)
Ethnomedicinal practices of Kol tribes in Similipal Biosphere Reserve, Orissa, India
/ S.D Rout and H.N. Thatoi / Ethnobotanical Leaflets 13: 379-87. 2009.
(29)

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