MEDICAL RATIONALE OF

LIVOKURE, HEPATOPRETECTIVE

HERBAL FORMULATION

MANAGEMENT OF HEPATIC DISORDERS

LIVOKURETM :Corrects liver dysfunction.

LIVOKURETM :Is safe and provides anti-viral effect in infective hepatitis.

LIVOKURETM :Augments appetite by normalizing liver function.

LIVOKURETM :Is ideally suited for long term treatment.

LIVOKURETM :Gives protection in metabolic liver disorders.

HIGHLY EFFECTIVE IN THE MANAGEMENT OF:

  • Infective Hepatitis, Fatty Infiltration of liver, Anorexia. Alcoholic and Metabolic liver disorders, Constipation etc.

Livokure is well-researched and clinically proven herbal formulation to act effectively as a prophylaxis as well as curative drug to any kind of disorder affecting the healthy functioning of the liver, one of the vital organs of the body. In our daily living we can not escape factors like consumption of rich and spicy food, polluted drinking water, toxic medicines or possible attack from hepatitis virus. There is also an increasing trend towards consumption of alcohol. As well these actors continuously jeopardize functioning of the liver, there is every necessity to ensure a complete protective shield for this vital organ, which Livokure ensures in a safe and sound manner.

  • An essential co-prescription with hepato-toxic drugs, such as:

Antibiotics, Hypotensives, Oral Hypoglycemics, Analgesics, Guinolones, Anti-Tuberculous etc.

COMPOSITION:

Each 500 mg. Capsule contains :

Phyllanthus niruri (bhuiamla):100 mg

Picrorhiza kurroa (kutki):150 mg

Andrographis paniculata ( kalmegh):150 mg

Holarrhena antidysenterica( kurchi):100 mg

Excipient:qs

DOSE :

ADULTS: 1 to 2 capsules twice daily (before food) or as directed by the physician.

CHILDREN:Half of the adult dose.

Maintenance Dose: One Capsule twice daily.

Onset of Action: One to Two hours.

Duration of Action:Eight to Twelve hours.

SIDE EFFCT / TOXIC EFFECT:

Not found in the clinical trial. May safely be continued for a longer period.

CONTRAINDICATION :

Hypersensitivity to any of the ingredients.

PRESENTATION :

Strip of 10 capsules.

CLINICAL VALIDATION :

  • Successful clinical trial was conducted at J. B. Roy State Ayurvedic Medical College & Hospital, Govt. of West Bengal, Kolkata.
  • Livokure compound has completely antagonized the toxic effects of Paracetamol on certain enzymes in serums as well as in isolated hepatic cells. Andrographolide has been found to be more potent.
  • The plant p. Kurroa has been found to be having hepatoprotective activities against alcohol, ccl4 and aflatoxin b1 induced hepatic damage. (ref.1).
  • Amoebicidal, anti-tuberculous and other anti-protozoal activity of individual alkaloids specially, conessine (kurchi) have been extensively investigated. (ref.2).

References:

1)Indigenous Drugs Of India (1982), 2nd Edition Academic Publishers, Calcutta; P – 343-344.

2)Cultivation and Utilization Of Medicinal Plants. (1982) Rrl, Jammu-Tawi, P-33.

MODE OF ACTION:

Livokure contains the mixture of picroside I and kutkoside, which has significant hepatopretective activity and the antiviral effect.

Livokure contains the active principle of andrographolide, which acts as a cholagogue, and is used in sluggishness of liver and jaundice.

Livokure containing lignans blocks DNA polymerase, the enzyme needed for the hepatitis B virus to reproduce. This is effective in jaundice and also for diarrhoea, dysentery and dyspepsia.

CHEMICAL CONSTITUENTS

AND

PHARMACOLOGICAL ACTIVITIES

OF EACH INGREDIENT OF LIVOKURE

Andrographis paniculata Nees

BOTANICAL NAME:Andrographis paniculata Nees

COMMON NAME :Bengali: Kalmeg, English: The Creat; Sanskrit: Kalmegha, Bhunimba

FAMILY:Acanthaceae

PARTS USED:Leaf

HABITAT :It grows abundantly in south eastern Asia, India (and Sri Lanka), Pakistan and Indonesia It grows "serpentine soil," which is relatively high in aluminum, copper and zinc.

DESCRIPTION OF PLANT:

Andrographis paniculata is an annual - branched, erect - running 1/2 to 1 meter in height.

Stem dark green, 0.3 - 1.0 m in height, 2 - 6 mm in diameter, quadrangular with longitudinal furrows and wings on the angles of the younger parts, slightly enlarged at the nodes; leaves glabrous, up to 8.0 cm long and 2.5 cm broad, lanceolate, pinnate; flowers small, in lax spreading axillary and terminal racemes or panicles; capsules linear-oblong, acute at both ends, 1.9 cm x 0.3 cm; seeds numerous, sub quadrate, yellowish brown. (Sing, A., Kapoor, L.D., and Chandra, V., Pharmaco-botanic studies of kalmegh, J. ResIndian Med., 7,93,1972)

Photograph 1: whole plant

CHEMICAL CONSTITUENTS:

The highest concentration of the active components is found just before the plant blooms.

The leaves contain the highest amount of andrographolide (2.39%), the most medicinally active phytochemical in the plant, while the seeds contain the lowest. (Sharma, A., L. Krishan, and S.S. Handa. 1992. Standardization of the Indian crude drug Kalmegh by high pressure liquid chromatographic determination of andrographolide. Phytochemical analysis 3:129-31). The other medicinal chemicals are also bitter principles: diterpenoids viz. deoxyandrographolide, -19ß-D-glucoside, and neo-andrographolide, all of which have been isolated from the leaves. (Chem Weiming and Liang Xiaotion. Deoxyandrographolide 19ß-D-glucoside from the leaves of A. paniculata, Planta Medica 1982; 15: 245-246.).
The primary medicinal component of Andrographis is andrographolide It has a very bitter taste, is a colourless crystalline in appearance, and is called a "diterpene lactone" - other active components include 14-deoxy-11,12- didehydroandrographolide (andrographlide D), homoandrographolide, andrographan, andrographon, andrographosterin, and stigmasterol - the last of which was isolated from an Astrographis preparation (Siripong, P., B. Kongkathip, K. Preechanukool, P. Picha, K. Tunsuwan, and W.C. Taylor. 1992. Cytotoxic diterpenoid constituents from Andrographis paniculata, Nees leaves, J. Sci. Soc. Thailand 18(4):187-94.).

The roots gave apigenin- 7, 4'- di-O-methyl ether, andrographolide and a new natural flavone, 5-hydroxy 7,8,2',3'- tetramethoxy flavone (C19H18O7, mp 150-151˚C; yield, 0.006%). They also contain a monohydroxy trimethyl flavone, andrographin (C18H16O6, mp 190-191˚C) and a dihydroxy-di-methoxyflavone, panicolin (C17H4O6, mp 263-264˚C). The presence of α-sitosterol is also reported. (Chemistry and pharmacology of Andrographis species' by Sudhanshu Saxena et al published in Indian Drugs35 (8) August 1998).

PHARMACOLOGICAL ACTION:

Andrographis paniculata, (AP), also known commonly as "King of Bitters," is a member of the plant family Acanthaceae, and has been used for centuries in Asia to treat GI tract and upper respiratory infections, fever, herpes, sore throat, and a variety of other chronic and infectious diseases. It is found in the Indian Pharmacopoeia and is the prominent in at least 26 Ayurvedic formulas.

Since ancient times, A. paniculata is used as a wonder drug in traditional Siddha and Ayurvedic systems of medicine as well as in tribal medicine in India and some other countries for multiple clinical applications. The therapeutic value of Kalmegh is due to its mechanism of action which is perhaps by enzyme induction. The plant extracts exhibits antityphoid and antifungal activities. Kalmegh is also reported to possess antihepatotoxic, antibiotic (Gupta et al., 1993), antimalarial, antihepatitic (Jayaram et al., 1989; Ramfi et al., 1992), antithrombogenic, Jaundice (Tomar et al., 1983), anti-inflammatory (Tajuddin et al., 1983; Shen et al., 2000), antisnakevenom, and antipyretic properties to mention a few, besides its general use as an immuno-stimulant agent. A recent study conducted at Bastyr University, USA confirms anti-HIV activity of andrographolide.

Liver & Gallbladder Protection:
In Ayurvedic medicine (a system used in India), there are 26 different formulations containing AP that are used to treat liver disorders. AP's four related medicinal compounds were tested for a protective effect against liver toxicity produced in mice by giving them carbon tetrachloride (a cleaning solvent), alcohol, or other toxic chemicals. (Kapil, A., I.B. Koul, S.K. Banerjee, and B.D. Gupta. 1993. Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochemical Pharmacology 46(1):182-85. ). These chemicals damage the liver by causing lipid peroxidation. This is a process whereby free radicals (reactive molecules) produced by the chemical attack and destroy cellular membranes that surround liver cells. When the AP compounds were given to animals three days before the toxic chemicals, there was a significant protective effect in the liver. This effect was attributed to the antioxidant ability of the AP compounds, which was effective as silymarin (another plant antioxidant from milk thistle).

In another study, andrographolide from AP was shown to produce a significant increase in bile flow. (Shukla, B., P.K.S. Visen, G.K. Patnaik, and B.N. Dhawan. 1992. Choleretic effect of andrographolide in rats and guinea pigs. Planta Med. 58:146-48. ). Bile is produced in the liver and stored in the gallbladder and aids in digestion. When a chemical, paracetamol, was given to animals pretreated with andrographolide, the usual decrease in bile production seen with this chemical was prevented. In this case. andrographolide was more potent than silymarin.

Infective hepatitis is an acute inflammatory condition of the liver. It is often followed by liver cirrhosis and may progress to a coma and death. In India, where ancient physicians used AP to treat similar liver ailments, a study was conducted to evaluate the effect of AP in infective hepatitis. There was marked improvement in the majority of patients tested, when given a decoction or infusion of AP. Appetite improved on the fifth day of treatment, jaundice (yellow colour of conjunctive of the eye and skin) gradually diminished and completely disappeared within 24 days, and fever subsided after 7 days on average. Other indications of effectiveness of AP included improvement in liver function tests. The researchers concluded that AP was a useful remedy for treatment of infective hepatitis.

The andrographolides present in AP are potent stimulators of gallbladder function. In animal experiments, those that received andrographolides for seven consecutive days showed an increase in bile flow, bile salts, and bile acids. These increases are beneficial and result in enhanced gallbladder function. Use of AP might, therefore, decrease the probability of gallstone formation and might also aid fat digestion. The andrographolides also prevented decreases in the amount of bile that are caused by acetaminophen toxicity. (Holt, Stephen M.D., Linda Comac, Miracle Herbs: How Herbs Combine with Modern Medicine to Treat Cancer, Heart Disease, AIDS, and More, Caro Publishing Group, 1998.).

REFERENCES:

  1. Chem Weiming and Liang Xiaotion. Deoxyandrographolide 19ß-D-glucoside from the leaves of A. paniculata, Planta Medica 1982; 15: 245-246.
  2. Chemistry and pharmacology of Andrographis species' by Sudhanshu Saxena et al published in Indian Drugs35 (8) August 1998
  3. Gupta et al., 1993
  4. Holt, Stephen M.D., Linda Comac, Miracle Herbs: How Herbs Combine with Modern Medicine to Treat Cancer, Heart Disease, AIDS, and More, Caro Publishing Group, 1998.).
  5. Jayaram et al., 1989; Ramfi et al., 1992
  6. Kapil, A., I.B. Koul, S.K. Banerjee, and B.D. Gupta. 1993. Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochemical Pharmacology 46(1):182-85.
  7. Sharma, A., L. Krishan, and S.S. Handa. 1992. Standardization of the Indian crude drug Kalmegh by high pressure liquid chromatographic determination of andrographolide. Phytochemical analysis 3:129-31
  8. Shukla, B., P.K.S. Visen, G.K. Patnaik, and B.N. Dhawan. 1992. Choleretic effect of andrographolide in rats and guinea pigs. Planta Med. 58:146-48.
  9. Siripong, P., B. Kongkathip, K. Preechanukool, P. Picha, K. Tunsuwan, and W.C. Taylor. 1992. Cytotoxic diterpenoid constituents from Andrographis paniculata, Nees leaves, J. Sci. Soc. Thailand 18(4):187-94.
  10. Sing,A.,Kapoor,L.D.,and Chandra, V., Pharmaco-botanic studies of kalmegh, J.ResIndian Med .,7,93,1972
  11. Tajuddin et al., 1983; Shen et al., 2000
  12. Tomar et al., 1983

Holarrhena antidysenterica Wal.

SCIENTIFIC NAME:Holarrhena antidysentericaWal.

COMMON NAME :Kurchi (Bengali); Ieory tree (English); Kureya (Hindi);

FAMILY:Apocynaceae.

PARTS USED :Bark.

HABITAT : It grows throughout India up to an altitude of 4,000 ft. It is especially abundant in the sub-Himalayan tract

DESCRIPTION:

A shrub or small tree, glabrous or pubescent, bark with pale. Leaves 10-20 by 5.11 cm from broadly ovate to elliptic, obtuse. Flowen white in terminal corymbose eymes, white. Fruit follicles of 20-38 cm long. A tall perennial woody plant have a main trunk and branches forming a distinct elevated crown; includes both gymnosperms and angiosperms. This is a small tree, glabrous or pubescent, bark with pale colour. Leaves 10-20 by 5.11 cm from broadly ovate to elliptic, obtuse. Flowers white in terminal corymbose eymes, white. Fruit follicles of 20-38 cm long (Ref: Indian Journal of Pharmaceutical Sciences (Scientific Publication of the Indian Pharmaceutical Association) March April 2002 Poonam G. Daswani Tannaz J. Birdi D. S. Antarkar1 and N. H. Antia. The Foundation for Medical Research Mumbai Holarrhena antidysenterica (L).

Fig.1 Portion of a flowering twig

Photograph-1&2: Whole plant

CHEMICAL CONSTITUENTS:

  1. Around 30 alkaloids have been isolated from the plant, mostly from the bark. These include conessine, kurchine, kurchicine, holarrhimine, conarrhimine, conaine, conessimine, iso-conessimine, conimine, holacetin and conkurchin. Aminoglycosides are important; the bark also gave nonalkaloids.(Ref: Indian J. Chem., 1981, 20B: 62.).
  1. Three new bases isolated from bark are conesi'mine, holarrhine and holarrhimine'. Further, two new alkaloids from the. seeds and bark were isolated -conimine and isoconessimine".The gum resin contains caoutechoue, lettoresinol-A and lettoresinol-B'. The formulation Kutajarishta has been studied for distribution of alkaloids.
  1. The principal alkaloid of kurchi is conessine. The other alkaloids reported to be present in the bark are: conamine, conkurchine, connessimine, kurchine, conarrhinine, holarrhinene and isoconcessimine

PHARMACOLOGICAL ACTIVITIES:

  1. The bark is used as an astringent, anthelmintic, antidontalgic, stomachic, febrifuge, antidropsical, diuretic, in piles, colic, dyspepsia, chest affections and as a remedy in diseases of the skin and spleen. It is a well known drug for amoebic dysentery and other gastric disorders. It is also indicated in diarrhoea, indigestion, flatulence and colic. [Ref: Dictionary of Indian Medicinal Plants, CIMAP, Lucknow (1992) ,Singh, K.P.: Ancient Sci. Life 5:228 (1986) , Selected Medicinal Plants of India, CHEMEXCIL, Mumbai (1982). ]
  1. Conessine from the bark killed free living amoebae and also kills Entamoeba histolytica in the dysenteric stools of experimentally infected kittens. It is markedly lethal to the flagellate protozoon. It is antitubercular also. Conkurchine is hydrochloride hypotensive and vasodilator. (Ref: J.Pharm. (London), 1049, 1:340. ,
  1. Antibacterial activity of Holarrhena antidysenterica [kurchi] Against The Enteric pathogens. The present study was undertaken to find the anti-bacterial activity of the crude aqueous and alcoholicextracts of stem bark of Holarrhena antidysentericaagainst the known enteric pathogens. Our present work suggests that clinical trial of both aque-ous and alcoholic extracts of the stem bark of H.antidysenterica can be carried out against a batteryof enteric pathogens, casuative agents of diarrheain infants and adults. (Ref: M. BALLAL, D. SRUJAN, K.K. BHAT,A. SHIRWAIKAR, P.G. SHIVANANDA Department of Microbiology, Kasturibai Medical college, Manipal Department of Botany, Poorna Prajna College, Udupi,Department of Chemistry, Kasturibai Medical College, Manipal-576 119.) (Ref:Indian Journal of Pharmacology 2001; 33: 392-393, Brown HC. Holarrhena antidysenterica. Br Med J 1992; 306:903-10).
  1. Investigation of the Antidiarrhoeal activity of holarrhena antidysenterica. Holarrhena antidysenterica (L)- Apocyanaceae, well known for its antidiarrhoeal activity was studied for its effect on diarrhoeagenic Escherichia Escherichia coil. Different dilutions of the decoction of the plant were assayed for its effect on the adherence and toxin production of 2 groups of E. coli enteropathogenic (EPEC) and enterotoxigenic (ETEC.) Adherence per se was not affected though disruption of the characteristic `microcolonies' of EPEC on HEp-2 cell line was observed. The decoction was more effective in inhibiting stable toxin production as compared with labile toxin. (Ref: Daswani PG; Birdi TJ; Antarkar DS; AntiaNH. Indian Journal of Pharmaceutical Sciences. 2002 Mar-Apr; 64(2): 164-7).
  1. Chopra and his associates (1972) showed that conessine killed free living amoebae, proteus and limax in dilutions of 1 in 2,80,000. Its action on the vegetative forms of E.histolytica was tested on the dysenteric stools of experimentally infected kittens. In mucus flakes in such stools motile amoebae were killed in dilutions of 1 in 2,80,000 in 8 minutes in the presence of an alkali and in 18 minutes in the absence of alkali, as compared with 1 in 2,00,000 of emetine. (Ref: Chopra, R. N.: Indigenous Drugs of India, Acadernic Publishers, Calcutta (1982).
  1. Conessine from the bark kills free living amoebae; it also kills Entamoeba histolytica in dysenteric stools of experimentally infected kittens. Conessine produces little effect on Trichomonas hominis but is lethal to the flagellate protozoon.
  1. In a clinical study on 40 cases of amoebiasis and giardiasis, the efficacy of Holarrhena antidysenterica in intestinal amoebiasis was 70%. Good response was also observed in Entamoeba histolytica cyst-passers, when treated with H. antidysenterica bark. (Ref:Encyclopedia of Indian Medicinal Plants – C.P.Khare. Published by Springer-VerlagBerlinHeidelberg, Printed in Germany.

REFERENCES:

1. Chopra, R. N.: Indigenous Drugs of India, Acadernic Publishers, Calcutta (1982).

2. Prasad, S. and P. N. Kaul,: Ind. J. Pharm, Oct. 423 (1956).

3. Anandakumar, A. et al.: Ancient Sci. Life 3: 203 (1983).306:903-10.

4. Roy, A. C. and Mukherjee,. J. Sci. Indus. Res. 17A: 158 (1958).

5. Siddiqui, S. and Pillai: Ind. J. Chem. Soc. 9: 553 (1932).

6. Siddiqui, S. et al.: J. Sci. Indus. Res. 25: 20 (1982).

7. Peacock and Choudbury: J. Chem. Soc. 1129 (1935).

8. Singh, K. P.: Ancient Sci. Life 5: 228 (1986).

9. Khorana, M. L. and T. N. Vasudevan: Ind. J. Pharin. 29: 149 (1967).

10. Chopra, R. N.: Indigenous Drugs of India, Acadernic Publishers, Calcutta (1982). Daswani PG; Birdi TJ; Antarkar DS; AntiaNH. Indian Journal of Pharmaceutical Sciences. 2002 Mar-Apr; 64(2): 164-7

11. Dictionary of Indian Medicinal Plants,CIMAP, Lucknow(1992) ,Singh, K.P.: Ancient Sci. Life 5:228 (1986) , Selected Medicinal Plants of India, CHEMEXCIL, Mumbai (1982).

12. Encyclopedia of Indian Medicinal Plants – C.P.Khare. Published by Springer-VerlagBerlinHeidelberg, Printed in Germany.

13. Indian J. Chem., 1981, 20B: 62.

14. Indian Journal of Pharmacology 2001; 33: 392-393, Brown HC. Holarrhena antidysenterica. Br Med J 1992; J.Pharm. (London), 1049, 1:340.

Phyllanthus niruri

BOTANICAL NAME: Phyllanthus niruri

FAMILY: Euphorbiaceae

SYNONYMS:Phyllanthus carolinianus, P, sellowianus,

COMMON NAMES:Chanca piedra

PART USED:Entire plant

HABIT:Shrubs, trees, and annual or biennial herbs

HABITAT :Distributed throughout the tropical and subtropical regions of both hemispheres.

DESCRIPTION OF PLANT:

Phyllanthus niruri is an annual, herb; height varies between 30–60 cm. Stem is angular with numerous distichous, elliptic-oblong leaves. Flowers are yellow and very numerous; monoecious with 1–3 staminate flowers and solitary pistillate flower borne axillary. Fruits capsule, very small, globose, smooth, seeds 3-gonous, longitudinally ribbed on the back. Seed to seed cycle occurs in two or four weeks. The flowering time in Indian conditions is July to August. Keys for identification of different species of Phyllanthus are found in Caius (1986), Agharkar (1991), and Gupta (984).

Fig: 1 Portion of Phyllanthus niruri

Fig: 2 Inflorescence

Photograph: Whole plant

CHEMICAL CONSTITUENTS: