Liver diseases - Part I

Developmentof

Novel Phyto-drugsin

Curing LIVER Diseases

Presented by Dr. Sudhakar KokateDirector PPRC, India

PPRC/INDIA 01

Liver‽ Largest organ in the human body

‽ Pivotal role in maintenance of health and

homeostasis

‽ Involved in vital functions –- Metabolism- Secretion- Storage- Detoxification of drugs & xenobiotics

PPRC/INDIA 02

Origin of Liver diseases(Acute & Chronic)

‽ Viruses

‽ Drugs

‽ Exposure to solvents

‽ Hydrocarbons

‽ Toxins

‽ Metabolic disorders

‽ Genetic disorders

‽ Alcohol consumption

PPRC/INDIA 03

Stat of Diseases

‽ Hepatitis A….In children 85 – 95 % in SE Asia

‽ Hepatitis B….5 – 7 %

‽ Hepatitis C….2 %

‽ Cirrhosis & Cancer….20 – 30 %

‽ Alcoholic hepatitis….60 %

‽ Hepato-toxicity….1 in 10,000 – 1 in 100,000

PPRC/INDIA 04

Phyto-Stat for Cure

‽ Hepato-protective plants….101 plants of

Globe….150 phyto-constituents

‽ India….87 plants….33 patented herbal formulations

‽ A number of poly-herbal mixtures

‽ In U.S. >13 % patients on herbal remedy

‽ Other countries range 18 – 65 %

PPRC/INDIA 05

Classification of Liver disorders

‽ Hepatitis

‽ Hepatosis

‽ Liver cirrhosis

‽ Liver injury

‽ Acute hepatitis

PPRC/INDIA 06

Classification of Liver disorders

‽ Chronic active Hepatitis B

‽ Primary Sclerosing Cholangitis (PSC)

‽ Primary Biliary Cirrhosis (PBC)

‽ Alcoholic fibrosis

‽ Alcoholic hepatitis

PPRC/INDIA 07

‽ Silybum marinum

‽ Picrorhiza kurroa

‽ Liv. 52: - Capparis spinosa - Cassia occidentalis

- Achillea millefolium - Tamarix gallica

- Cichorium intybus - Solanum nigrum

- Terminalia arjuna

Well characterised phyto-drugs

PPRC/INDIA 08

‽ T J 9: Prescribed in China, Japan as “Sho-saiko-to” – an

aqueous extract from the roots of Scutellaria,

Glycyrrhiza, Bupleurum, Ginseng, Pinella tuber, Jujube

fruit & ginger

‽ Compound 861: Chinese medicine with 10 defined

herbs, main plants – Salvia miltiorrhiza, Astragalus

membranaceous, Spatholobus suferectus

Well characterised phyto-drugs

Emerging research trendOn

Phyto-medicine

PPRC/INDIA 09

Andrographis paniculata

PPRC/INDIA 10

Andrographis paniculata

‽ Habitat: Plains of India

‽ Extensively used in Unani and Ayurveda

‽ Aqueous extract of leaves …. Effective

‽ The extract inhibited BHC induced Liver toxicity in

Swiss male mice …. Trivedi & Rawal, 2000

PPRC/INDIA 11

Boerhavia diffusa

PPRC/INDIA 12

Boerhavia diffusa

‽ Commonly known as “Punarnava”

‽ Perennial creeping herb found in waste lands of

India

‽ Roots effective in Liver Diseases …. Kirtikar & Basu

1933, Chopra 1956

PPRC/INDIA 13

Boerhavia diffusa

‽ Whole plant extract potent in cure …. Chakraborti &

Handa 1989

‽ Compounds Punarnavin, Beta-sitosterol from roots

Beta-D-glucoside, tetracosanoic, hexacosanoic,

stearic, palmitic, arachidic acid, hentriacontane,

ursolic acid punarnavoside

PPRC/INDIA 14

Peumus boldus

PPRC/INDIA 15

Peumus boldus

‽ Indigenous to Chile

‽ Small tree: 8 cm long, coriaceous texture, strong

odour

‽ Family: Monimiaceae

‽ Chemicals: Boldine, Ascaridole, Linalool, P-cymene

cineole

PPRC/INDIA 16

Fumaria indica

PPRC/INDIA 17

Fumaria indica

‽ The whole plant: Constituent of Unani, Ayurvedic

and Medicinal preparations

‽ Family: Fumariaceae

‽ Anti-hepatotoxic against thioacetamide in vitro &

carbon tetrachloride, paracetamol, rifampicin

‽ Active principle: similar to Silymarin

PPRC/INDIA 18

Fumaria indica

‽ The plant is useful in:

- Blood purification

- Cutaneous diseases

- Obstructions of Liver

PPRC/INDIA 19

Curcuma longa

PPRC/INDIA 20

Curcuma longa

‽ Hepato-protective against carbon tetra chloride,

paracetamol and Aspergillus aflatoxin

‽ Effective due to anti-oxidant property

‽ Major metabolite of Curcumin – tetrahydrocurcumin

(THC)

‽ THC prevents erythromycin estolate induced Liver

disease

PPRC/INDIA 21

Picrorhiza kurroa

PPRC/INDIA 22

Picrorhiza kurroa

‽ Family: Scrophulariaceae

‽ Small perennial herb

‽ Grows in northwest India

‽ Active principle: irioid glycoside, Picrosides I, II, III,

Kutkoside

‽ Hepato-protective effect superior to that of Silymarin in

many cases

PPRC/INDIA 23

Picrorhiza kurroa

‽ Protects Liver cells from a wide variety of injuries

including:

- Carbon tetrachloride (Santra et. al 1998) -

- Galactosamine (Dwivedi 1992)

- Ethanol (Rastogi et. al 1996)

- Acetaminophen (Singh et. al 1992)

- Thioacetamide (Dwivedi et. al 1991)

PPRC/INDIA 24

Phyllanthus amarus

PPRC/INDIA 25

Phyllanthus amarus

‽ Family: Euphorbiaceae

‽ Widespread throughout tropic and subtropics in sandy

regions or cultivated & wastelands

‽ The plant is bitter, astringent, cooling, diuretic,

stomachic, febrifuge & antiseptic

‽ Butanol fraction of the whole plant exhibited potent

activity (Tripathi et. al 1992)

PPRC/INDIA 26

Phyllanthus amarus

‽ Whole plant powder 0.66 gm/kg in rat showed hepato-

protective action against carbon tetrachloride (Sane et.

al 1955)

‽ Albino rats treated with ethanol were orally given

whole plant powder 200 mg/rat per day for 45 days

showed significant activity

PPRC/INDIA 27

Glycyrrhiza glabra

PPRC/INDIA 28

Glycyrrhiza glabra

‽ Glycyrrhizin, main component of Licorice root

‽ Found to be effective for chronic hepatitis and liver

cirrhosis

‽ It showed hepato-protective effect against toxicity by

carbon tetrachloride and Gal N

‽ Antioxidant properties of glycyrrhizin & glycyrrhetinic

acid responsible for anti-hepatotoxic activity

PPRC/INDIA 29

Silybum marianum

PPRC/INDIA 30

Silybum marianum

‽ Most characterised useful important plant

‽ Mixture of Silvbin, Silvdianin & Silychristin

‽ Significant action against induction by carbon

tetrachloride of Liver damage in rats

‽ It reduces the prolongation of hexa-harbital

sleeping time produced by carbon tetrachloride

PPRC/INDIA 31

Cichorium intybus

PPRC/INDIA 32

Cichorium intybus

‽ Family: Compositae

‽ Aqueous extract showed hepato-protective toxicity

induced by carbon tetrachloride & paracetamol

(Gadgoli & Mishra 1995)

‽ Scientists conducted several experiments on this

plant

PPRC/INDIA 33

Tinospora cordifolia

PPRC/INDIA 34

Tinospora cordifolia

‽ Commonly known as Guduchi or Amrita

‽ Most valuable medicinal herb in Ayurveda

‽ Plant has ability to impart youthfulness vitality &

longevity

‽ Also quite effective in Liver injury

PPRC/INDIA 35

Tinospora cordifolia

‽ In modern times it is well known as hepato-

protective, adaptogenic & immuno-modulatory

activities

‽ Clinical studies in patients of hepatitis showed that

Guduchi plays an important role in relieving the

symptoms of Liver disease

PPRC/INDIA 36

Wedelia calendulacea

PPRC/INDIA 37

Wedelia calendulacea

‽ Family: Compositae

‽ Perennial herb with light camphor-like odour

‽ Traditionally used as tonic, spleen enlargement and

skin diseases

‽ Showed protective action in Paracetamol induced

Liver damage

PPRC/INDIA 38

Wedelia calendulacea

‽ The alcoholic extract of whole plant exhibited

protection against carbon tetrachloride

‽ The extract increased bile flow in rats.

‽ Min. lethal dose was greater than 200 mg/kg P.O. in

mice

PPRC/INDIA 39

Tephrosia purpurea

PPRC/INDIA 40

Tephrosia purpurea

‽ Locally known as “Sarapunkha”

‽ Most important ingredient of formulations available in

Indian market for liver ailments

‽ Good results in Cirrhosis & vital Hepatitis in clinical trials

‽ It prevents cellular leakage & loss of functional integrity

of Liver cell membranes, release in hepatic regeneration

PPRC/INDIA 41

Protium heptaphyllum

PPRC/INDIA 42

Protium heptaphyllum

‽ Family: Burseraceae

‽ Active principle: alpha & beta amyrin, a triterpene

mixture

‽ Folk medicinal plant

‽ It protects acetaminophen induced Liver injury

PPRC/INDIA 43

Buddleja officinalis

PPRC/INDIA 44

Buddleja officinalis

‽ Family: Loganiaceae

‽ Flowers, buds effective

‽ Active principle: Acteoside, a phenylethanoid

glycoside

‽ Possesses antioxidant property

‽ Protects against carbon tetrachloride

PPRC/INDIA 45

Anastatica hierochuntica

PPRC/INDIA 46

Anastatica hierochuntica

‽ Egyptian medicinal herb

‽ Chemicals: Anastatins A & B from Methanolic

extract

‽ Protective against d-galactosamine induced

cytotoxicity in primary cultured mouse

‽ Activity is stronger than that of commercial Silybin

PPRC/INDIA 47

Tilia argentea

PPRC/INDIA 48

Tilia argentea

‽ Methanolic ext. showed protection against d-

galactosamine, Lipopolysaccharide induced Liver

injury in mice

‽ Flowers are effective hepato-protectors

PPRC/INDIA 49

Garcinia kola

PPRC/INDIA 50

Garcinia kola

‽ Extract of seeds of this plant showed protection

against carbon tetrachloride induced Liver injury

‽ Extensively studied plant

PPRC/INDIA 51

Hymenaea martiana

PPRC/INDIA 52

Hymenaea martiana

‽ Active principle: Astibin

‽ Protects against carbon tetrachloride induced Liver

injury

‽ One of the important useful herb

Thank You !!

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