[go: up one dir, main page]

WO2009064156A1 - Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice - Google Patents

Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice Download PDF

Info

Publication number
WO2009064156A1
WO2009064156A1 PCT/MY2007/000079 MY2007000079W WO2009064156A1 WO 2009064156 A1 WO2009064156 A1 WO 2009064156A1 MY 2007000079 W MY2007000079 W MY 2007000079W WO 2009064156 A1 WO2009064156 A1 WO 2009064156A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
labisia pumila
inhibited
maximum effect
product produced
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/MY2007/000079
Other languages
English (en)
Other versions
WO2009064156A8 (fr
Inventor
Ghulam Nabi Qazi
Sarang Bani
Anpurna Kaul
Anjali Pandey
Kiranjeet Kour
Surrinder Koul
Bishan Dutt Gupta
Pyarelal Sangwan
Ravinder Kumar Raina
Rajendran Manickavasagar
Balkrishnan Chandan
Prashant Singh Chandan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Council of Scientific and Industrial Research CSIR
HOLISTA BIOTECHNOLOGY Sdn Bhd
Original Assignee
Council of Scientific and Industrial Research CSIR
HOLISTA BIOTECHNOLOGY Sdn Bhd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Council of Scientific and Industrial Research CSIR, HOLISTA BIOTECHNOLOGY Sdn Bhd filed Critical Council of Scientific and Industrial Research CSIR
Priority to PCT/MY2007/000079 priority Critical patent/WO2009064156A1/fr
Publication of WO2009064156A1 publication Critical patent/WO2009064156A1/fr
Anticipated expiration legal-status Critical
Publication of WO2009064156A8 publication Critical patent/WO2009064156A8/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Definitions

  • the present invention relates generally to a process for preparation of plant extract and more particularly to the process for preparation of water-soluble Labisia pumila extract. Further the present invention also relates to a composition or pharmaceutical preparation obtained from Labisia pumila extract for the preparation of a medicament relating to hepatoprotective activity.
  • Labisia pumila family: Myrsinaceae
  • Kacip Fatimah has been used by many generation of Malay women to induce and facilitate childbirth as well as a post-partum medicine.
  • This study was undertaken to investigate the activity of the aqueous leaf extract from Labisia pumila leaves (LPPM/A0031) on liver in experimental animals.Liver has a pivotal role in regulation of physiological processes. Toxic chemicals and infections mainly cause liver diseases. Hepatocyte alterations of various origins result in acute and chronic dysfunctions, which may be lethal [Decker K. and Keppler D. Rev.
  • liver disorders are still the major hazard both in urban and rural population.
  • no specific treatment for liver ailments is available except a few herbal preparations, WHO, Regional Office Manila, 1993.; [Subeamoniam and Pushpangadan, Indian Journal of Pharmacology, 31,166-175 (1999)].
  • WHO Regional Office Manila, 1993.
  • Pushpangadan Indian Journal of Pharmacology, 31,166-175 (1999)].
  • hepatotoxin that causes acute hepatitis should have close resemblance with the viral hepatitis, clinically, biochemically and histologically.
  • drug induced hepatitis proves indistinguishable from viral hepatitis.
  • Chemically induced hepatic injury for experimental studies should be severe enough to cause death or to modify hepatic function.
  • the mechanism of acute hepatic injury depends upon the chemical compound and the species of animals used. Many chemicals produce parenchymal damage (cytotoxic injury), arrest bile flow and cause jaundice. The damage may be acquired or toxicological phenonmenon, therapeutic misadventure or induced experimentally. Drugs also cause chronic hepatic diseases such as hepatitis, fatty liver, cirrhosis, and several vascular lesions of the liver.
  • hepatoprotective agents it is the role of hepatoprotective agents to interfere with these pathological processes by blocking their evolution and helping recovery by preventing hepatocytes degeneration, necrosis, steatosis and inflammation, stimulate regeneration processes, and inhibit fibrosis which leads to cirrhosis and death [Doreswamy, R., Sharma, D., Indian Drugs, 32, 139-144 (1995)], Kumar et al, Cell injury and adaptation. In: "Basic Pathology", 5.sup.th Edn. Prime Books (pvt.) Ltd., Banglore, India. 1992, pp. 3-24.
  • Acute hepatitis closely resembling viral hepatitis clinically, biochemically and histologically, can be produced by chemicals and drugs in humans and experimental animals, [AL-Tuwaijiri A. et al Heptology, 51: 107-113 (1981); Decker K. and Keppler D. Rev Physiol. Biochem. Pharmacol., 71, 79-106 (1974); Kumar et al, Cell injury and adaptation. In: "Basic Pathology", 5.sub.th Edn. Prime Books (Pvt.)Ltd.,Bangalore,India.l992,pp.3-24].
  • the object of the invention relates process for preparation of Labisia pumila extract by extracting dried Labisia pumila plant material with water to form a water- soluble extract and drying the extract obtained, characterized in that the extract having the capability to develop a composition for hepatoprotective activity.
  • the process is preferred to include the following steps isolating extracts obtained from Labisia pumila; obtaining powdered leaves from the Labisia pumila with double distilled water or distilled water (1:8) using accelerated solvent extraction at 40-80 0 C for up to 30 minutes, draining off the solid plant material and recharging with equal volume of fresh solvent three times more, combining and concentrating the extracts to produce a free flowing solid with the extractive value of up to 12%;obtaining a composition comprising the extracts.
  • the present invention also relates to an extract or extracts obtained from Labisia pumila plant, wherein the said extract or extracts according to any having the capability of hepatoprotective activity.
  • the present invention also describes a product produced from the extract, wherein elevated levels of aspartate aminotransferase where inhibited with a maximum effect observed at 500mg/kg p.o where it was 52.80% against hepatitis control.
  • the product also elevates levels of alkaline phosphate where inhibited with a maximum effect observed at 500mg/kg p.o where it was 35.70% against hepatitis control; elevates levels of bilirubin where inhibited with a maximum effect observed at 500mg/kg p.o where it was 30.64% against hepatitis control; elevates levels of gluthione where inhibited with a maximum effect observed at 500mg/kg p.o where it was 39.49% against hepatitis control; elevates levels of lipidperoxide where inhibited with a maximum effect observed at 500mg/kg p.o where it was 38.73% against hepatitis control.77 ⁇ e product also provides TGF-betal is preferably
  • the product also inhibits hepatitis induced elevated levels of proinflammatory cytokines like TNF-alpha and EL-6.
  • the present invention also provides uses of the extract obtained from Labisia pumila plant for the preparation of a medicament or pharmaceutical preparations for hepatoprotective activity BRIEF DESCRIPTION OF THE DRAWINGS
  • Figure 1 represents Effect of different doses of LPPM/A003 on TGF-beta 1 expression
  • Figure 2 represents Effect of different doses of LPPM/ A003 on IL-6 expression
  • Figure 3 represents Effect of different doses of LPPM/A003 on TNF-alpha expression
  • the main object of the present invention is to develop a composition comprising extract from plant Labisia pumila having hepatoprotective activity.
  • the composition in this present invention is obtained from Labisia pumila plant extract.
  • the present invention also relates to a process for isolating the extract from the plant.
  • Yet another object of the present invention is to develop a method of producing a composition comprising extract from plant Labisia pumila having hepatoprotection activity.
  • Still another object of the present invention is to develop a method of treating a subject including animals and/or humans for hepatoprotection, using a composition comprising extract from plant Labisia pumila with a hepatoprotective activity as compared to commercially available hepatoprotective drugs.
  • the present invention is preferably used as a potent hepato protectant having a broad spectrum activity. Further to that the invention is also capable of inhibiting ALT, AST and ALP enzymes that are elevated in hepatic damage tissues.
  • the composition in the present invention also has the capability to inhibited hepatitis induced elevated levels of TGF-betal which provides a substantially important activity in pathogenesis of fibrosis in hepatitis.
  • the composition also has the capability to be use as an inhibitor of hepatitis wherein the composition induces the levels of proinflammatory cytokines like TNF-alpha and IL-6.
  • 1 Kg of Labisia pumila dried leaf powder is extracted with millipore/ double distilled water/ distilled water (1:8) and heated at 80 0 C for 3 hours, the contents drained off and the solid plant material recharged with equal volume of fresh solvent (water). The process repeated three times more. All the combined extracts then concentrated on rotavapor under reduced pressure at 50 0 C to give free flowing solid (extractive value -10%).
  • 1 Kg of Labisia pumila dried leaf powder is extracted with millipore/ double distilled water/ distilled water (1:8) and heated at 80 0 C for 3 hours, the contents drained off and the solid plant material recharged with equal volume of fresh solvent (water). The process repeated three times more. All the combined extracts then lyophilized to give free flowing solid (extractive value -9.5%).
  • the aqueous extract of Labisia pumila prepared by taking three sets each comprising of powdered leaves (fresh or dried) with millipore/ double distilled water/ distilled water (1:8) using accelerated solvent extraction with temperature
  • the aqueous extract of Labisia pumila prepared by taking three sets each comprising of powdered leaves (fresh or dried) with millipore/ double distilled water/ distilled water (1:8) using accelerated solvent extraction with temperature
  • mice The acute oral toxicity studies were carried out following OECD guidelines No.423 in mice. The animals were observed individually periodically during the first 24 h, with special attention given during the first 4 h, and daily thereafter, for a total of 14 days, simultaneously. A single dose of LPPM/A003 administered orally to each group of female mice did not show any change in gross general behaviour of these test animals. A single dose of 5000mg/kg p.o. was also evaluated. No mortality or any change in normal behaviour was observed at this high dose.
  • Hepatoprotective activity of LPPM/ A003 is presented in the Tablel&2.
  • Administration of CCl 4 and GaIN results in marked elevation of ALT, AST and ALP. The damaged cell liberates these enzymes into systematic circulation.
  • GaIN and CCl 4 administration also causes hyperbilirubinaemia, one of the most useful clues to the severity of necrosis and hepatic damage.
  • Treatment with LPPM/A003 reversed the increased levels of ALT, AST and ALP depicting protective effect. Results clearly demonstrate LPPM/A003 to be the most active at a high tested dose level of 500mg/kg, p. o. which is well comparable to silymarin.
  • Reactive metabolite formed by number of drug and chemicals e.g. CCl 4 are detoxified by conjugation with glutathione. Excessive accumulation of toxic metabolites results in accelerated lipid peroxidation and drastic fall in hepatic GSH content.
  • LPPM A003 significantly reversed the increased lipid peroxidation and maintained hepatic GSH. The above results demonstrate that LPPM/ A003 has an impressive hepatoprotective effect on acute liver injury induced by CCl 4 and GaIN.
  • Values represent the mean ⁇ SE and within parentheses hepatoprotective activity percent of si> animals per group.
  • Values represent the mean ⁇ SE and within parenthesis hepatoprotective activity percent of six animals per group.
  • TGF-Bl Transforming growth factor ⁇ 1
  • TNF- ⁇ Tumor necrosis factor-alpha
  • EL-6 Interleukin 6
  • Hepatic fibrosis is characterized by abnormally excessive accumulation of extracellular matrix (ECM) accompanied by exaggerated cytokine releasing.
  • ECM extracellular matrix
  • TGF-beta Transforming growth factor-beta
  • TGF-betal signaling plays an important role in the pathogenesis of fibrosis in hepatitis.
  • Values represent the mean ⁇ SE for six animals and within parenthesis Activity percent against the CCl 4 induced group .

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne d'une manière générale un procédé permettant de préparer un extrait de plante et, plus précisément, le procédé de préparation de l'extrait de Labisia pumila hydrosoluble. L'invention concerne également une composition ou une préparation pharmaceutique obtenue à partir d'extrait de Libisia pumila destiné à la préparation d'un médicament se rapportant à l'activité hépatoprotectrice.
PCT/MY2007/000079 2007-11-15 2007-11-15 Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice Ceased WO2009064156A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/MY2007/000079 WO2009064156A1 (fr) 2007-11-15 2007-11-15 Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/MY2007/000079 WO2009064156A1 (fr) 2007-11-15 2007-11-15 Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice

Publications (2)

Publication Number Publication Date
WO2009064156A1 true WO2009064156A1 (fr) 2009-05-22
WO2009064156A8 WO2009064156A8 (fr) 2011-11-24

Family

ID=40638916

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/MY2007/000079 Ceased WO2009064156A1 (fr) 2007-11-15 2007-11-15 Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice

Country Status (1)

Country Link
WO (1) WO2009064156A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010147449A1 (fr) * 2009-06-16 2010-12-23 Holista Biotech Sdn. Bhd. Activité adaptogène d'un extrait de labisia pumila
WO2013112040A1 (fr) 2012-01-27 2013-08-01 Biotropics Malaysia Berhad Utilisation de certains dérivés de benzène trioxigéné dans la gestion de graisse corporelle

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070082069A1 (en) * 2005-10-12 2007-04-12 Gov't Of Malaysia, As Rep. By The Ministry Of Science, Technology And Innovation Process for preparation of labisia pumila extract

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070082069A1 (en) * 2005-10-12 2007-04-12 Gov't Of Malaysia, As Rep. By The Ministry Of Science, Technology And Innovation Process for preparation of labisia pumila extract

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
EFFENDY A. W. M ET AL.: "The Side Effects ofKacip Fatimah Extract on Liver and Kidney of White Rats.", JOURNAL OF SUSTAINABILITY SCIENCE AND MANAGEMENT, vol. 1, no. 1, 2006, pages 40 - 46 *
FUAD W.E.M ET AL.: "Evaluation of the Teratogenicity of Aqueous Extract of Labisia pumila var. alata in Rats.", MALAYSIAN JOURNAL OF MEDICAL SCIENCES, vol. 12, no. 2, July 2005 (2005-07-01), pages 13 - 21 *
SHAHRIM Z. ET AL.: "The in vivo Rodent Micronucleus assay of Kacip Fatimah (Labisia pumila) Extract.", TROPICAL BIOMEDICINE, vol. 23, no. 2, 2006, pages 214 - 219 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010147449A1 (fr) * 2009-06-16 2010-12-23 Holista Biotech Sdn. Bhd. Activité adaptogène d'un extrait de labisia pumila
WO2013112040A1 (fr) 2012-01-27 2013-08-01 Biotropics Malaysia Berhad Utilisation de certains dérivés de benzène trioxigéné dans la gestion de graisse corporelle

Also Published As

Publication number Publication date
WO2009064156A8 (fr) 2011-11-24

Similar Documents

Publication Publication Date Title
Pari et al. Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats
KR20180101460A (ko) 근육의 보호에서 시스탄케 투불로사 추출물 및 이소악테오사이드의 용도
Sadeque et al. Comparative efficacy of dried fruits of Carica papaya Linn. and Vitamin-E on preventing hepatotoxicity in rats
Sadeque et al. Protective effect of dried fruits of Carica papaya on hepatotoxicity in rat
WO2009064156A1 (fr) Nouvelle composition obtenue à partir d'extrait de labisia pumila pour activité hépaprotectrice
Naser et al. Analgesic effect of silymarin in chicks.
RU2701567C1 (ru) Средство, обладающее гепатопротекторной активностью
JP5609834B2 (ja) リパーゼ阻害剤
Sangeetha et al. A review on traditional herb Portulaca oleracea
KR101051076B1 (ko) 개복숭아를 포함하는 알레르기 치료용 조성물 및 이의 제조방법
Bharskar Review on phytochemistry and pharmacological aspects of Pedalium murex Linn
KR20100087825A (ko) 타우린 및 플라보노이드가 함유된 숙취해소제
KR20150036880A (ko) 곤드레 추출물을 포함하는 고지혈증 개선용 조성물 및 이의 제조방법
Asadu et al. In vivo toxicological studies on methanol leaf extract of Lantana Camara
CN1057158A (zh) 植物病毒病防治剂
CN103181930A (zh) 五味子蜂花粉有效部位及其在预防肝脏损伤中的应用
KR101824329B1 (ko) 목단피 추출물의 분획물을 포함하는 간질환의 예방 또는 치료용 조성물
KR20170099105A (ko) 모과, 감초 및 두릅의 혼합 추출물을 유효성분으로 포함하는 염증성 통증의 완화, 예방 또는 치료용 조성물
Abdel-Latif et al. Hepatoprotective effect of coumarin and chlorophyll against aflatoxicosis in rat
JPH09255583A (ja) 抗かゆみ剤
KR100778942B1 (ko) 항염증 효과를 나타내는 소나무잔나비버섯 추출물 및 그용도
Pingale Hepatosuppression by Adhatoda vasica against CCl4 Induced Liver Toxicity in Rat
KR100377789B1 (ko) 간섬유화 및 간경화 치료 및 예방용 의약 조성물
EP1207894A1 (fr) Composition synergique pour le traitement du foie et des troubles associes au foie et son procede de preparation
CN1457794A (zh) 胡黄连及其环烯醚萜总甙提取物的新用途

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07834526

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 4687/DELNP/2009

Country of ref document: IN

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: PI 2010002279

Country of ref document: MY

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 31.08.2010)

122 Ep: pct application non-entry in european phase

Ref document number: 07834526

Country of ref document: EP

Kind code of ref document: A1