disease is a leading cause of death in many countries and the causative
factors are alcohol consumption, malnutrition, aneamia, hepatotoxic
drugs and infections etc. The liver, a vital organ instrumental
in metabolism, detoxification and elimination, is responsible for
protection of human body against adverse effects of drugs, chemicals,
toxins, bacteria, viruses and parasites etc., but in the process
liver itself is under threat and obviously needs protection.
far no effective measures are available for the treatment of liver
diseases. The different medical, surgical and therapeutic methods
used at present are inadequate with generally poor results. Also
some of the modern drugs which are given to treat liver diseases
may themselves cause liver damage.
is therefore, imperative to search alternative drugs for the treatment
of liver diseases to replace the existing currently used drugs of
doubtful efficacy and safety.
Phytochemical investigation and antihepatotoxic activity of
marianum Linn. (Carduus marianus), family: Asteraceae, a medicinal
plant widely used in traditional European medicine for the treatment
of various liver ailment, was selected for phytochemical and pharmacological
investigation to establish the efficacy of plant extracts, and various
isolated constituents as potent antihepatotoxic agent.
Kg seeds of S. marianum were dried and crushed to coarse powder
which was then exhaustively extracted with ethanol by cold percolation.
The crude alcoholic extract was fractionated into Pet. Ether (900
gm), Ethyl acetate (800 gm) and Methanol (300 gm) soluble fraction
different compounds like silybin a1, silybina2, silybin b1, silybin
b2, and various steroids were isolated and characterized on the
basis of IR, UV, NMR and Mass spectral data.
of the isolated compound, silybin was treated with Boron trifluoride
in diethyl ether and change in stereochemistry was studied. The
studies suggested that proton of ring C of silybin became Trans
from Cis, and orientation of proton at position 8 in
1, 4 dioxane ring also changed from b to a.
various extracts and isolated compounds were evaluated for antihepatotoxic
activity in albino rats by using CCl4 as toxicant. The degree of
protection was measured by performing histopathological studies
and by estimating various biochemical parameters. Like SGOT, SGPT,
ALKP, TP & TA. The methanolic extract showed good antihepatotoxic
activity, which was comparable to effects produced by standard drug
silybon- 70. The other two extracts, Pet. ether and ethyl acetate
also showed moderate protection.
the isolated compounds showed better protection than standard drug,
however among all the isolated compounds, SK 16 and SK-1 were
found to be most potent antihepatotoxic compounds.
Synthesis and antihepatotoxic activity of compounds containing
1,4 dioxane ring system:
(silybon-70), a hepatoprotective drug is a mixture of three isomers
namely silybin, silychristin and silydianin. Among the three isomers
silybin is the most potent antihepatotoxic agent. On analyzing the
chemical structure of 3 isomers, it was observed that silybin contains
1,4 dioxane ring system in its structure, however this ring is absent
in other two isomers. Thus the hepatoprotective activity possessed
by silybin can be attributed to the presence of 1,4 dioxane ring
system in its strucuture.
We therefore, thought worthwhile that 1,4 dioxane ring system might
play an important role in exhibiting antihepatotoxic activity. Thus
on the basis of above finding a number of heterocyclic compounds
like flavones, xanthones, coumarins and chalcones etc. possessing
1,4 dioxane ring in their molecule were synthesized. The synthesized
compounds were screened for antihepatotoxic activity against CCl4
intoxicated albino rats, by estimating biochemical parameters. The
synthesized compounds were simple, low molecular weight and could
be easily synthesized in lab. For incorporating 1,4 dioxane ring
the free ortho dihydroxy compounds were condensed with either ethylene
bromide to obtain unsubstituted benzo 1,4 dioxane derivatives or
with epichlorohydrin to obtain 2- hydroxymethyl benzo 1,4 dioxane
derivatives in presence of aq. Alkali.
the synthesized compounds the flavono dioxins were found to be the
most potent compounds as they decreased the elevated levels of SGOT,
SGPT, ALKP and TA, and increased the decreased level of TP. The
effects produced by flavono dioxins were comparable to standard
drug silybon 70. The dioxino coumarins showed moderate results followed
by dioxino xanthones and chalocone derivatives.
above studies suggested that both flavone moiety and 1,4 dioxane
ring along with 2- hydroxy methyl group in the side chain could
exhibit potent antihepatotoxic activity and in turn could be used
for treatment of various ailments of liver. The synthesized compounds
are low molecular weight and could be easily prepared. On the other
hand silybin is a complex molecule and thus can not be prepared
easily. Furthermore the synthesized compounds are expected to be
easily metabolizable in comparison to silymarin, being simple and
low molecular weight