ABOUT PHYLLANTHUS
Pharmacology References
Clinical study
- Genus
Phyllanthus for chronic hepatitis B virus infection:
a systematic review.
Liu J, Lin H, McIntosh H. J Viral Hepat 2001
Sep;8(5):358-66
- A comparative
study of Phyllanthus amarus compound and interferon
in the treatment of chronic viral hepatitis B.
Xin-Hua W, Chang-Qing L, Xing-Bo G, Lin-Chun
F. Southeast Asian J Trop Med Public Health 2001;32(1):140
- Effect of
Phyllanthus amarus on chronic carriers of hepatitis
B virus.
Thyagarajan SP, Subramanian S, Thirunalasundari
T, Venkateswaran PS, Blumberg BS. Lancet 1988 Oct 1;2(8614):764-6
- Phyllanthus
combination plus lamivudin in treatment of 40 cases of chronic
hepatitis B.
Zhang, JJ, Wang, HJ, Zhang, H. Journal of Shandong
University of TCM, China
Laboratory
Research paper
- A review
of the plants of the genus Phyllanthus: their
chemistry, pharmacology, and therapeutic potential.
Calixto JB, Santos AR, Cechinel Filho V, Yunes
RA. Med Res Rev 1998 Jul;18(4):225-58
- Treatment
of chronic liver diseases with traditional Chinese medicine.
Wang BE. J Gastroenterol Hepatol 2000 May;15
Suppl:E67-70
- Screening
of antiviral agents from medicinal herbs by means of Hepadnaviruses
models
Mi Z, Chen H, Zhang X, Li Z, Chen W, Shao X.
Zhongguo Zhong Yao Za Zhi 1997 Jan;22(1):43-5, 63
- The in-vitro
inactivation of HBsAg by extracts of plants in the genus
Phyllanthus
del Barrio Alonso G, Caballero Perez O, Chevalier
P. Rev Cubana Med Trop 1995;47(2):127-30
- Phyllanthus
amarus suppresses hepatitis B virus by interrupting interactions
between HBV enhancer I and cellular transcription factors.
Ott M, Thyagarajan SP, Gupta S. Eur J Clin Invest
1997 Nov;27(11):908-15
- Phyllanthus
amarus down-regulates HBV mRNA transcription and replication.
Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk
RD, Gupta S. Eur J Clin Invest 1996 Dec;26(12):1069-76
- Inhibition
of HBsAg secretion from Alexander cell line by Phyllanthus
amarus.
Jayaram S, Thyagarajan SP. Indian J Pathol Microbiol
1996 Jul;39(3):211-5
- Experimental
study on anti-duck hepatitis B viral effect of Phyllanthus
urinaria of different areas and combined therapy with
other drugs
Chen YX, Guo SH, Zhang DF. Zhongguo Zhong Xi
Yi Jie He Za Zhi 1995 Apr;15(4):225-7
- Evaluation
of anti-hepadnavirus activity ofPhyllanthus amarus
and Phyllanthus maderaspatensis in duck hepatitis
B virus carrier Pekin ducks.
Munshi A, Mehrotra R, Ramesh R, Panda SK. J Med
Virol 1993 Dec;41(4):275-81
- Effects of
extract from Phyllanthus urinaria on HBsAg production
in PLC/PRF/5 cell line
Ji XH, Qin YZ, Wang WY, Zhu JY, Liu XT. Zhongguo
Zhong Yao Za Zhi 1993 Aug;18(8):496-8, 511
- Effect of
an extract from Phyllanthus amarus on hepatitis
B surface antigen gene expression in human hepatoma cells.
Yeh SF, Hong CY, Huang YL, Liu TY, Choo KB,
Chou CK. Antiviral Res 1993 Mar;20(3):185-92
- Effects of
Phyllanthus plant extracts on duck hepatitis B virus
in vitro and in vivo.
Shead A, Vickery K, Pajkos A, Medhurst R, Freiman
J, Dixon R, Cossart Y. Antiviral Res 1992 Jun;18(2):127-38
- In vitro
effect of Phyllanthus amarus on hepatitis B virus.
Mehrotra R, Rawat S, Kulshreshtha DK, Goyal
P, Patnaik GK, Dhawan BN. Indian J Med Res 1991 Mar;93:71-3
- Effect of
Phyllanthus amarus on duck hepatitis B virus replication
in vivo.
Niu JZ, Wang YY, Qiao M, Gowans E, Edwards P,
Thyagarajan SP, Gust I, Locarnini S. J Med Virol 1990 Dec;32(4):212-8
- In vitro
studies on the effect of certain natural products against hepatitis
B virus.
Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik
GK, Dhawan BN. Indian J Med Res 1990 Apr;92:133-8
- HBV and hepatocellular
carcinoma-treatment of HBV carriers with Phyllanthus
amarus.
Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan
SP. Cancer Detect Prev 1989;14(2):195-201
- Effects of
an extract from Phyllanthus niruri on hepatitis
B and woodchuck hepatitis viruses: in vitro and in vivo studies.
Venkateswaran PS, Millman I, Blumberg BS. Proc
Natl Acad Sci U S A 1987 Jan;84(1):274-8
- In Vitro
Inactivation of HbsAg. by Eclipta alba Hassk and Phyllanthus
niruri.
Indian J Med Res 76 (Suppl) Dec 1982, 124-30.
- Comparative
hepatoprotective activity of three Phyllanthus Species,
P. urinaria, P. niruri and P. simplex, on carbon tetrachloride-induced
liver injury in the rat
A. Prakash, K.S. Satyan, S.P. Wahi, and R.P.
Singh. Phototherapy Research Vol. 9, 594-596, 1995.
- Effect of
Emblica officinalis, Phyllanthus amarus and Picrorrhiza
kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis.
Jeena KJ, Joy KL, Kuttan R. Cancer Lett 1999
Feb 8;136(1):11-6
- Effects of
Phyllanthus urinaria L. on human hepatoma cells.
Wang CJ, Yuan DP, Chen W, et al. Shenzen J.
of Traditional Chinese Medicine Research. 1997. Vol. 8 (6):
499
- General studies
of Chinese medicine and its active ingredient in anti-viral
hepatitis.
Shee Kan & She RH. Chinese Herbal Medicine.
1994. Vol. 25(7): 381-2
- Herbal medicines
for liver diseases in India.
Thyagarajan S, Jayaram S, Gopalakrishnan V,
Hari R, Jeyakumar P, Sripathi M. J Gastroenterol Hepatol 2002
Dec;17 Suppl 3:S370-S376
- Mechanism
of protective action of Phyllanthus against injuries
of liver cells.
Zhou S, Xu C, Zhou N, Huang Y, Huang , et al.
Zhongguo Zhong Yao Za Zhi 1997 Feb;22(2):109-11
- Phyllanthus
amarus extract administration increases the life span
of rats with hepatocellular carcinoma.
Rajeshkumar NV, Kuttan R. J Ethnopharmacol 2000
Nov;73(1-2):215-9
- Protective
effect of Phyllanthus against CCl4 -induced mitochondrial dysfunction.
Padma P, Setty OH. Life Sci 1999;64(25):2411-7
- Protective
effect of Phyllanthus against ethanol-induced
mitochondrial dysfunction.
Sebastian T, Setty OH. Alcohol 1999 Jan;17(1):29-34
- Screening
of Phyllanthus niruri Linn. And Ricinus communis
Linn. On alcohol-induced liver cell damage in non-hepatomized
and partially hepatictomized rats.
Shyam SA, Arun G & Sarla, A. Indian J. of Pharmacology.
1986. 18(14): 211-214.
- Study of
Phyllanthus product inhibition effect on mice liver
cancer.
Yang SL, Guang SH & Zhu YT. Journal of Cancer.
2000. Vol. 19(8) 837-838.
Traditionally
uses
- A survey
of medicinal plants of Minas Gerais, Brazil
G. Schmeda Hirschmann and A. Rojas de Arias.
Jour of Ethnopharm, 29, 1990, 159-172.
- Amazonian
Ethnobotanical Dictionary
James Alan Duke and Rodolfo Vasquez, 1994, by
CRC Press.
- Antihepatotoxic
principles of Phyllanthus niruri herbs.
Syamasundar KV, Singh B, Thakur RS, Husain A,
Kiso Y, Hikino H.
- Usage and
bioassays in Phyllanthus. IV. Clustering of antiviral
uses and other effects.
Unander DW, Webster GL, Blumberg BS. J Ethnopharmacol
1995 Jan;45(1):1-18
Clinical study
1.Genus
Phyllanthus for chronic hepatitis B virus infection:
a systematic review.
Liu J, Lin H, McIntosh H. J Viral Hepat 2001 Sep;8(5):358-66
Twenty-two randomized trials (n=1947) were identified.
The methodological quality was high in five double-blind
trials and low in the 17 remaining trials. The combined
results showed that Phyllanthus species had positive
effect on clearance of serum HBsAg (relative risk 5.64,
95% CI 1.85-17.21) compared with placebo or no intervention.
Phyllanthus species were better than nonspecific
treatment or other herbal medicines for the clearance of
serum HBsAg, HBeAg, HBV DNA, and liver enzyme normalization.
No serious adverse event was reported... |
2. A
comparative study of Phyllanthus amarus compound
and interferon in the treatment of chronic viral hepatitis
B.
Xin-Hua W, Chang-Qing L, Xing-Bo G, Lin-Chun F. Southeast
Asian J Trop Med Public Health 2001;32(1):140
Fifty-five patients with chronic viral hepatitis B were
randomly divided into two groups. Thirty patients were treated
with Phyllanthus amarus compound (PA Co) for three
months in the treatment group, another 25 patients were
treated with domestic recombinant human interferon alpha-1b
(IFN-alpha 1b) for three months as controls. The total effective
rate in the treatment group was 83.3%, showing no significant
difference from the control (p>0.05). The normalization
rates of ALT, A/G and SB in the treatment group were 73.3%,
80.0% and 78.2% respectively, which were significantly higher
than that in the control (p<0.05). The negative conversion
rates of HBeAg and HBV-DNA in the treatment group were 42.3%
and 47.8%, showing no significant difference from the control
(p>0.005). It is indicated that PA Co has remarkable effect
for chronic viral hepatitis B in recovery of liver function
and inhibition of the replication of HBV. |
3. Effect
of Phyllanthus amarus on chronic carriers
of hepatitis B virus.
Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran
PS, Blumberg BS. Lancet 1988 Oct 1;2(8614):764-6
In a preliminary study, carriers of hepatitis B virus
were treated with a preparation of the plant Phyllanthus
amarus for 30 days. 22 of 37 (59%) treated patients
had lost hepatitis B surface antigen when tested 15-20 days
after the end of the treatment compared with only 1 of 23
(4%) placebo-treated controls. Some subjects have been followed
for up to 9 months. In no case has the surface antigen returned.
Clinical observation revealed few or no toxic effects. The
encouraging results of this preliminary study recommend
continued evaluation of this plant and the active principles
isolated from it. |
4. Phyllanthus
combination plus lamivudin in treatment of 40 cases of
chronic hepatitis B.
Zhang, JJ, Wang, HJ, Zhang, H. Journal of Shandong University
of TCM, China
Phyllanthus
niruri has been demonstrated to have inhibition effect
on HBV replication, increases immune system, significantly
reduce enzymes levels due to CCl4-induced liver injury,
inhibits liver free radical formation and repair liver cells.
Phyllanthus has stronger effect on immune system
and liver function but not so effective against HBV replication.
Combination of both treatments can lead to a synergetic
effect and result has showed that the PHCo plus lamivudin
has a better effect compared to lamivudin alone |
Laboratory
Research paper
- A
review of the plants of the genus Phyllanthus: their
chemistry, pharmacology, and therapeutic potential.
Calixto JB, Santos AR, Cechinel Filho V, Yunes RA. Med Res Rev
1998 Jul;18(4):225-58
The plants of the genus Phyllanthus are widely distributed
in most tropical and subtropical countries, and have long
been used in folk medicine to treat kidney and urinary bladder
disturbances, intestinal infections, diabetes, and hepatitis
B. Recently, the interest in the plants has increased considerably.
Substantial progress on their chemical, pharmacological properties,
and a few clinical studies of some Phyllanthus species
have been made. This review discusses the current knowledge
of their chemistry, the in vitro and in vivo pharmacological,
biochemical, and clinical studies carried out on the extracts,
and the main active constituents isolated from different species
of plants of the genus Phyllanthus. These studies carried
out with the extracts and purified compounds from these plants
support most of their reported uses in folk medicine as an
antiviral, in the treatment of genitourinary disorders, and
as antinociceptive agents. Several compounds including alkaloids,
flavonoids, lignans, phenols, and terpenes were isolated from
these plants and some of them interact with most key enzymes.
Together this data strongly supports the view that Phyllanthus
have potential beneficial therapeutic actions in the management
of hepatitis B, nefrolitiase, and in painful disorders.
- Treatment
of chronic liver diseases with traditional Chinese medicine.
Wang BE. J Gastroenterol Hepatol 2000 May;15 Suppl:E67-70
Traditional Chinese medicine is still being extensively
used for treatment of liver disease in China. The anti-viral
herbs, Phyllanthus amarus, P. niruri and P. urninaria,
and Oxymatrine extracted from Sophora flavecientis and S.
subprostratae, have been shown to have a remarkable HBV suppressing
effect with a serum conversion rate for HBeAg and HBV DNA
around 45%, similar to that of IFN-alpha.
- Screening
of antiviral agents from medicinal herbs by means of Hepadnaviruses
models
Mi Z, Chen H, Zhang X, Li Z, Chen W, Shao X. Zhongguo Zhong
Yao Za Zhi 1997 Jan;22(1):43-5, 63
The antiviral study of 21 Chinese medicinal herbs was carried
out in vitro and in vivo. The extracts of Phyllanthus urinarin
and Polygonum cuspidatum exhibite obvious effects on duck
hepatitis B virus and human hepatitis B virus, while the extract
of Eclipta alba showed limited inhibition on HBV DAN polymerase.
- The
in-vitro inactivation of HBsAg by extracts of plants in the
genus Phyllanthus
del Barrio Alonso G, Caballero Perez O, Chevalier P. Rev Cubana
Med Trop 1995;47(2):127-30
Three species from the Phyllanthus genus coming from
the Cuban eastern zone were studied to determine the inactivation
capacity of the surface antigen (Ags HB) of in vitro hepatitis
B virus. Alcoholic extracts were prepared from each species
and from different parts of such plants, and sera from patients
positive to Ags HB were treated with them. Results demonstrate
that the analysed species own the capacity of inactivating
that antigen between the 93 and the 97% of the sera assayed.
The inactivation capacity analysis of the three parts of Phyllanthus
chamaecristoides revealed a greater activity in extracts from
the stems (97%) with a behavior resembling the two incubation
temperatures used. The presence of flavonoids in the extract
of this species is observed.
- Phyllanthus
amarus suppresses hepatitis B virus by interrupting interactions
between HBV enhancer I and cellular transcription factors.
Ott M, Thyagarajan SP, Gupta S. Eur J Clin Invest 1997 Nov;27(11):908-15
The Phyllanthus amarus plant suppresses HBV mRNA
transcription in vitro and exhibits therapeutic potential
in chronic HBV carriers. Analysis in HuH-7 cells with transfected
plasmids using a luciferase reporter showed that P. amarus
specifically inhibited HBV enhancer I activity. To identify
the mechanism of this HBV enhancer I inhibition, liver-enriched
cellular transcription factors were co-expressed in HuH-7
cells. The C/EBP alpha and beta, as well as HNF-3 alpha and
beta transcription factors, significantly up-regulated the
HBV enhancer I activity. In contrast, co-transfection of HNF-I
alpha or beta had no effect upon the HBV enhancer I activity.
Exposure to P. amarus inhibited C/EBP alpha- and beta-mediated
up-regulation of HBV enhancer I activity in a dose-dependent
manner, whereas HNF-3 alpha- and beta-mediated up-regulation
of HBV enhancer I was unaffected. In vitro gel shifts showed
that P. amarus inhibited complexing of C/EBP transcription
factors to a consensus oligonucleotide sequence, whereas DNA
binding of AP-1 and SP-1 transcription factors was unaffected.
As P. amarus down-regulates HBV mRNA transcription by a specific
mechanism involving interactions between HBV enhancer I and
C/EBP transcription factors, purification and further analysis
of the active P. amarus component will advance insights into
its antiviral activity.
- Phyllanthus
amarus down-regulates HBV mRNA transcription and replication.
Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S.
Eur J Clin Invest 1996 Dec;26(12):1069-76
The Phyllanthus amarus plant shows potential for
treating hepatitis B virus. To define the mechanism of action
of P. amarus, we used HepG2 2.2.15 cells, which support hepatitis
B virus replication. P. amarus inhibited hepatitis B virus
polymerase activity, decreased episomal hepatitis B virus
DNA content and suppressed virus release into culture medium.
To examine transcriptional control mechanisms, we used G26
hepatitis B virus transgenic mice, which produce serum HBsAg
but neither HBcAg nor virion particles. When P. amarus was
administered to transgenic mice, hepatic HBsAg mRNA levels
decreased, indicating transcriptional or post-transcriptional
down-regulation of the transgene. Increase in hepatitis B
virus mRNA expression after stimulation of the glucocorticoid
responsive element was also suppressed by P. amarus, suggesting
involvement of the hepatitis B virus enhancer in this response.
Disruption by P. amarus of hepatitis B virus polymerase activity,
mRNA transcription and replication supports its role as an
antiviral agent.
- Inhibition
of HBsAg secretion from Alexander cell line by Phyllanthus
amarus.
Jayaram S, Thyagarajan SP. Indian J Pathol Microbiol 1996 Jul;39(3):211-5
Alexander cell line, an human hepatocellular carcinoma derived
cell line which has the property of secreting HBsAg in the
supernatant was used to study the antiviral property of P.
amarus. Aquous extract of P. amarus was evaluated for its
in vitro ability to inhibit HBsAg secretion on a dose dependent
manner. It was seen that P. amarus at 1mg/ml concentration
on a single dose inhibited the secretion of HBsAg for a period
of 48 hours. This experiment proved the anti hepatitis B virus
property of P. amarus at cellular level and further confirmed
its beneficial use in the treatment of acute and chronic hepatitis
B and healthy carriers of HBV.
- Experimental
study on anti-duck hepatitis B viral effect of Phyllanthus
urinaria of different areas and combined therapy with
other drugs
Chen YX, Guo SH, Zhang DF. Zhongguo Zhong Xi Yi Jie He Za Zhi
1995 Apr;15(4):225-7
The duck hepatitis B virus model was treated with Phyllanthus
urinaria of different area and combined with Sophora flavesceus
as well as ciprofloxacin once a day for one month, the results
indicated: Guangxi and Yunnan Phyllanthus could lower
the serum DHBV DNA significantly (P < 0.05), but Chongqing
Phyllanthus couldn't. And the amount of serum DHBV
DNA rose a week after stopping of Yunnan Phyllanthus.
The antiviral effect of Guangxi Phyllanthus combined with
ciprofloxacin seems to be strengthened (P < 0.05).
- Evaluation
of anti-hepadnavirus activity ofPhyllanthus amarus
and Phyllanthus maderaspatensis in duck hepatitis
B virus carrier Pekin ducks.
Munshi A, Mehrotra R, Ramesh R, Panda SK. J Med Virol 1993 Dec;41(4):275-81
Extracts of the two traditional Indian herbs, Phyllanthus
amarus (P. amarus) and Phyllanthus maderaspatensis
(P. maderaspatensis), described by others as useful in the
treatment of chronic hepatitis B virus infection were studied
for antiviral properties on duck hepatitis B virus infection.
One hundred and fourteen ducks infected posthatch with the
duck hepatitis B virus (DHBV) were divided into groups at
three months of age and treated intraperitoneally with the
aqueous, butanol, and alcoholic extracts of these two plants
at doses of 25, 50, or 200 mg/kg body weight. Saline-treated
animals served as controls. In the ducks negative for DHBV
in serum after treatment, we observed replicative intermediates
in the liver. There was no definite antiviral property observed
in the treated ducks.
- Effects
of extract from Phyllanthus urinaria on HBsAg
production in PLC/PRF/5 cell line
Ji XH, Qin YZ, Wang WY, Zhu JY, Liu XT. Zhongguo Zhong Yao Za
Zhi 1993 Aug;18(8):496-8, 511
Experiment on the effect of extracts from P. urinaria on
HBsAg production in PLC/PRF/5 human hepatoma cell line showed
that the production was decreased markedly 48 hours after
the treatment of cells with 2-4 mg/ml P. urinaria, especially
in combination with 10(-5) mol/L of Ara-A. The decrease of
extracellular HB-sAg excretion seems to stem from the inhibition
of intracellular HBsAg formation.
- Effect
of an extract from Phyllanthus amarus on hepatitis
B surface antigen gene expression in human hepatoma cells.
Yeh SF, Hong CY, Huang YL, Liu TY, Choo KB, Chou CK. Antiviral
Res 1993 Mar;20(3):185-92
It has been suggested that Phyllanthus amarus may
be helpful in the treatment of hepatitis B virus infection.
We studied the effect of an aqueous extract of P. amarus on
the cultured hepatoma cell line HepA2. This cell line had
been transfected with tandemly arranged HBV DNA and continued
to synthesize and secrete both HBsAg and HBeAg. Extract of
P. amarus reversibly inhibited cellular proliferation and
suppressed HBsAg production but not HBeAg production in HepA2
cells. We also found that P. amarus suppressed HBsAg gene
expression at mRNA level in a time-dependent manner, and selectively
abolished the HBsAg gene promoter driven CAT activity. Our
results demonstrate that P. amarus contains some active components
which can suppress the HBsAg gene expression in human hepatoma
cells. Such suppression may contribute the antiviral activity
of P. amarus in vivo.
- Effects
of Phyllanthus plant extracts on duck hepatitis
B virus in vitro and in vivo.
Shead A, Vickery K, Pajkos A, Medhurst R, Freiman J, Dixon R,
Cossart Y. Antiviral Res 1992 Jun;18(2):127-38
The effects of extracts of five Australian Phyllanthus
species (P. hirtellus, P. gunnii, P. gasstroemii, P. similis
and P. tenellus), other plant extracts and the antiviral drug
foscarnet on duck hepatitis B virus (DHBV) endogenous DNA
polymerase (DNAp) activity were compared. All 5 Phyllanthus
species caused 50% inhibition at concentrations of dry weight
between 350-800 micrograms/ml, which is comparable with the
effect described for P. amarus on the DNAp of human and woodchuck
hepatitis B viruses. Incubation of P. hirtellus with 100 ID50
DHBV neutralized infection. However, neither P. gasstroemi
extract, given by intraperitoneal injection (i.p.) at a dose
of 20 mg/kg 3 times per week to ducklings early in the incubation
period, or P. hirtellus extract, given to established DHBV
carrier ducklings, prevented or eliminated infection.
- In
vitro effect of Phyllanthus amarus on hepatitis
B virus.
Mehrotra R, Rawat S, Kulshreshtha DK, Goyal P, Patnaik GK, Dhawan
BN. Indian J Med Res 1991 Mar;93:71-3
To evaluate the effects of P. amarus on hepatitis B virus
(HBV) antigens and HBV-DNA, initial ethanolic extract and
subsequent fractions of the plants were prepared. The whole
plant material was dried, powdered and extracted with alcohol
and subsequently fractionated in hexane, chloroform, butanol
and finally in water. All the material were tested for in
vitro effects on HBsAg, HBeAg and HBV-DNA in serum samples
positive for HBV antigens followed by the screening of respective
antigens by Elisa. HBV-DNA was determined by molecular hybridization.
The extracts were effective against HBV antigens, the butanol
extract being the most potent. Further chromatographic fractions
showed an enhanced activity. The active fractions inhibited
the interaction between HBsAg/HBeAg and their corresponding
antibodies suggesting anti-HBs, anti-HBe-like activity and
also an effect on HBV-DNA.
- Effect
of Phyllanthus amarus on duck hepatitis B virus
replication in vivo.
Niu JZ, Wang YY, Qiao M, Gowans E, Edwards P, Thyagarajan SP,
Gust I, Locarnini S. J Med Virol 1990 Dec;32(4):212-8
Nine ducks congenitally infected with the duck hepatitis
B virus (DHBV) were treated either orally (four ducks for
10 weeks) or intraperitoneally (five ducks for 12 weeks) with
the Indian traditional herbal remedy Phyllanthus amarus.
Compared to placebo-treated control ducks, these treatments
did not result in a reduction of circulating viral DNA in
the serum or in the level of viral DNA replication in the
liver. In two of the five intraperitoneal-treated ducks, a
reduction in the levels of duck hepatitis B surface antigenaemia
(DHBsAg) was observed. The data strongly suggest that Phyllanthus
amarus has no significant inhibitory effect on DHBV DNA
replication and only a minor effect on DHBsAg production.
- In
vitro studies on the effect of certain natural products against
hepatitis B virus.
Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN.
Indian J Med Res 1990 Apr;92:133-8
Picroliv (active principle from Picrorrhiza kurroa), its
major components picroside I, catalpol, kutkoside I, kutkoside,
andrographolide (active constituent of Andrographis paniculata),
silymarin and Phyllanthus niruri extract were tested
for the presence of anti hepatitis B virus surface antigen
(anti HBs) like activity. HBsAg positive serum samples obtained
from hepatitis B virus (HBV) associated acute and chronic
liver diseases and healthy HBsAg carriers were used to evaluate
the anti-HBs like activity of compounds/extract. The latter
were mixed with serum samples and incubated at 37 degrees
C overnight followed by HBsAg screening in the Elisa system.
A promising anti-HBsAg like activity was noted in picroliv
(and its major components) catalpol, P. niruri which differed
from the classical viral neutralization. Picroliv also inhibited
purified HBV antigens (HBsAg and HBsAg) prepared from healthy
HBsAg carriers. The in vitro testing system appears to be
a suitable model to identify an agent active against HBV,
prior to undertaking detailed studies.
- HBV
and hepatocellular carcinoma-treatment of HBV carriers with
Phyllanthus amarus.
Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Cancer
Detect Prev 1989;14(2):195-201
Extracts of Phyllanthus amarus inhibit the DNA polymerase
of HBV and related viruses. Woodchuck carriers of woodchuck
hepatitis virus (WHV) were treated intraperitoneally with
P. amarus extract. Three of four animals which had been recently
infected lost the virus. Animals infected for about 3 months
or more had a decrease in virus levels. Human carriers of
HBV were treated orally for 1 month. About 60% of the carriers
lost HBV, which did not return during the observation period.
Fractions containing active principles are now being isolated
and characterized.
- Effects
of an extract from Phyllanthus niruri on hepatitis
B and woodchuck hepatitis viruses: in vitro and in vivo studies.
Venkateswaran PS, Millman I, Blumberg BS. Proc Natl Acad Sci
U S A 1987 Jan;84(1):274-8
An aqueous extract of the plant Phyllanthus niruri
inhibits endogenous DNA polymerase of hepatitis B virus and
binds to the surface antigen of hepatitis B virus in vitro.
The extract also inhibits woodchuck hepatitis virus (WHV)
DNA polymerase and binds to the surface antigen of WHV in
vitro. The extract, nontoxic to mice, was tested for antiviral
activity in woodchucks (Marmota monax). In a trial using six
long-term WHV-carrier woodchucks, five treated animals showed
a faster decrease in woodchuck hepatitis virus surface antigen
titer compared to one untreated control. In animals recently
infected with WHV, the extract was effective when administered
i.p. in three out of four animals in reducing and within 3-6
weeks eliminating both the surface antigen titer and DNA polymerase
activity in serum. The treatment was discontinued after 10
weeks, and the treated animals have remained free of detectable
markers of WHV for more than 45 weeks. In contrast, three
untreated controls remained positive for both markers for
WHV. One of the controls died after 8 weeks; the other two
controls have remained positive for WHV markers for more than
45 weeks. In a third trial with long-term carriers, test animals
treated subcutaneously with the extract for 12 weeks did not
respond; but on switching the mode of administration to i.p.,
two out of the five animals showed a significant decrease
in woodchuck hepatitis virus surface antigen titer compared
to controls.
- In
Vitro Inactivation of HbsAg. by Eclipta alba Hassk and Phyllanthus
niruri.
Indian J Med Res 76 (Suppl) Dec 1982, 124-30.
Researchers did an in vitro test to evaluate the in vitro
immuno-inactivating ability of plants on hepatitis B surface
antigen. When P. niruri roots and shoots were dried and powdered,
the researchers revealed a definite immunoinactive property
of the plant against the surface antigen of hepatitis B virus.
Further analysis by TLC indicated a red pigment uniformly
present in all the parts of these plants to be the seat of
such action.
- Comparative
hepatoprotective activity of three Phyllanthus Species,
P. urinaria, P. niruri and P. simplex, on carbon tetrachloride-induced
liver injury in the rat
A. Prakash, K.S. Satyan, S.P. Wahi, and R.P. Singh. Phototherapy
Research Vol. 9, 594-596, 1995.
Pretreatment of animals with an alcoholic extract of P.
niruri showed it had significant hepatoprotective activity
at doses of 40mg/kg/day (p less than 0.05) and 400 mg/kg/day
(p < 0.01). Further, at the different doses administered,
the extracts showed dose-dependent hepatoprotective activity.
- Effect
of Emblica officinalis, Phyllanthus amarus and
Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis.
Jeena KJ, Joy KL, Kuttan R. Cancer Lett 1999 Feb 8;136(1):11-6
Extracts of Emblica officinalis (EO), Phyllanthus amarus
(P. amarus) and Picrorrhiza kurroa (P. kurroa) significantly
inhibited hepatocarcinogenesis induced by N-nitrosodiethylamine
(NDEA) in a dose dependent manner. The anticarcinogenic activity
of these extracts were evaluated by their effect on tumour
incidence, levels of carcinogen metabolizing enzymes, levels
of liver cancer markers and liver injury markers. Animals
treated with NDEA alone showed 100% tumour incidence and significantly
elevated tissue levels of drug metabolizing enzymes such as
glutathione S-transferase (GST) and aniline hydroxylase (AH).
Treatment of extracts significantly reduced these levels.
Levels of gamma-glutamyl transpeptidase (GGT) were also found
to be elevated both in serum and tissues of tumour bearing
animals, while they were significantly reduced in the treated
group. Similar reduction was seen in tissue levels of reduced
glutathione. Serum levels of lipid peroxide (LPO), alkaline
phosphatase (ALP) and glutamate pyruvate transaminase (OPT),
which are markers of liver injury, were also elevated. Morphology
of liver tissue and levels of marker enzymes indicated that
these extracts offered protection against chemical carcinogenesis.
- Effects
of Phyllanthus urinaria L. on human hepatoma cells.
Wang CJ, Yuan DP, Chen W, et al. Shenzen J. of Traditional Chinese
Medicine Research. 1997. Vol. 8 (6): 499
The effects of Phyllanthus urinaria L. on SMMC7221
of human hepatoma cells were studied. Human hepatoma cells
were treated with extractive of P. urinaria L. in vitro. The
survival activity and DNA synthesis of the cells were observed
by MTT assay and H-TdR incorporating test. Results showed
after treated with the extractive of P. urinaria, the survival
activities of SMMC7221 cells were obviously weakened and incorporation
rates of H-TdR decreased significantly, the inhibitory rates
on cell proliferation increased dose-dependently. P. urinaria
therefore had remarkable effects of inhibition on poliferation
as well as toxicities on human hepatoma cells.
- General
studies of Chinese medicine and its active ingredient in anti-viral
hepatitis.
Shee Kan & She RH. Chinese Herbal Medicine. 1994. Vol. 25(7):
381-2
Studies have shown Phyllanthus species are effective in
preventing hepatitis, liver cell protection and liver cancer
prevention. In vitro studies exhibit HBsAg inactivation activity
as well as HBV DNA, WHV DNA and DHBV DNAp inhibition activities.
- Herbal
medicines for liver diseases in India.
Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar
P, Sripathi M. J Gastroenterol Hepatol 2002 Dec;17 Suppl 3:S370-S376
The use of natural remedies for the treatment of liver diseases
has a long history, starting with the Ayurvedhic treatment,
and extending to the Chinese, European and other systems of
traditional medicines. The 21st century has seen a paradigm
shift towards therapeutic evaluation of herbal products in
liver diseases by carefully synergizing the strengths of the
traditional systems of medicine with that of the modern concept
of evidence-based medicinal evaluation, standardization of
herbal products and randomized placebo controlled clinical
trials to support clinical efficacy. In spite of the availability
of more than 300 preparations for the treatment of jaundice
and chronic liver diseases in Indian systems of medicine using
more than 87 Indian medicinal plants, only four terrestrial
plants have been scientifically elucidated while adhering
to the internationally acceptable scientific protocols. In-depth
studies have proved Sylibum marianum to be anti-oxidative,
antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating
and liver regenerative. Glycyrrhiza glabra has been shown
to be hepatoprotective and capable of inducing an indigenous
interferon. Picrorhiza kurroa is proved to be anti-inflammatory,
hepatoprotective and immunomodulatory. Extensive studies on
Phyllanthus amarus have confirmed this plant preparation
as being anti-viral against HBV and HVC, hepatoprotective
and immunomodulating, as well as possessing anti-inflammatory
properties. For the first time in the Indian systems of medicine,
a chemo-biological fingerprinting methodology for standardization
of P. amarus preparation has been patented.
- Mechanism
of protective action of Phyllanthus against injuries
of liver cells.
Zhou S, Xu C, Zhou N, Huang Y, Huang , et al. Zhongguo Zhong
Yao Za Zhi 1997 Feb;22(2):109-11
It has been found out that the carbon tetrachloride (CCl4)-induced
increase of serum glutamic-pyruvic transaminase (ALT) and
elevation of MDA in liver of mice are significantly lowered
by Phyllanthus in vivo, and the coincubation of isolated
rat hepatocytes with Phyllanthus in vitro significantly
inhibits CCl4-induced decrease of mobility of membrane of
liver cells and increase of intracellular free Ca2+ ([Ca2+]i)
concentrations of liver cells. These results suggest that
the anti-lipid peroxidation effect and protective action of
membrane of Phyllanthus may be related to its protective
action against CCl4-induced liver injuries.
- Phyllanthus
amarus extract administration increases the life span
of rats with hepatocellular carcinoma.
Rajeshkumar NV, Kuttan R. J Ethnopharmacol 2000 Nov;73(1-2):215-9
The effect of P. amarus extract administration after induction
of hepatocellular carcinoma (HCC) by N-nitrosodiethylamine
(NDEA) was studied in Wistar rats. Administration of an aqueous
extract of P. amarus was found to significantly increase the
survival of hepatocellular carcinoma harboring animals. P.
amarus administration was found to be ineffective in controlling
the liver weight, elevation of tissue gamma-glutamyl transpeptidase,
serum alkaline phosphatase and serum glutamate pyruvate transaminase
of HCC harboring animals.
- Protective
effect of Phyllanthus against CCl4 -induced mitochondrial dysfunction.
Padma P, Setty OH. Life Sci 1999;64(25):2411-7
The effect of CCl4 administration on liver mitochondrial
function and the protective effect of an aqueous extract of
Phyllanthus were studied in rats. The following changes were
observed in mitochondria due to the administration of CCl4.
1) A decrease in the rate of respiration, respiratory control
ratio and P/O ratio using glutamate and malate or succinate
as substrates. 2) A decrease in the activities of NADH dehydrogenase
(35%), succinate dehydrogenase (76%) and cytochrome c oxidase
(51%). The rate of electron transfer through site I, site
II and site III was studied independently and found to be
significantly decreased. 3) A decrease in the content of cytochrome
aa3 (34%). 4) A significant decrease in the levels of phospholipids
particularly cardiolipin and a significant increase in the
lipid peroxide level was observed. The CCl4 induced toxicity
may be partly due to the lipid peroxidation and partly due
to the effect on protein synthesis. Administration of rats
with an aqueous extract of Phyllanthus prior to CCl4 administration
showed significant protection on the carbon tetrachloride
induced mitochondrial dysfunction on all the parameters studied.
- Protective
effect of Phyllanthus against ethanol-induced
mitochondrial dysfunction.
Sebastian T, Setty OH. Alcohol 1999 Jan;17(1):29-34
Chronic ethanol consumption (10 g per kg body weight) significantly
decreased the rate of respiration, P/O ratio, and respiratory
control ratio (RCR). The activities of NADH dehydrogenase
and cytochrome oxidase were significantly decreased in submitochondrial
particles by ethanol administration compared to control. No
significant difference was observed in membrane potential
of submitochondrial particles. Cytochrome b, c and aa3 content
of mitochondria were significantly decreased by ethanol feeding.
Ethanol-induced inhibition on rate of respiration, P/O ratio,
and RCR was relieved to a great extent by the administration
of the aqueous extract of Phyllanthus (100 mg dry powder
of the plant per kg body weight) along with ethanol.
- Screening
of Phyllanthus niruri Linn. And Ricinus communis
Linn. On alcohol-induced liver cell damage in non-hepatomized
and partially hepatictomized rats.
Shyam SA, Arun G & Sarla, A. Indian J. of Pharmacology. 1986.
18(14): 211-214.
A new model of short duration for inducing hepatotoxicity
in rat has been developed by administrating Tohfa' a country
made liquor (28.5% of ethanol) to partially hepatectomized
(65-70%) rats orally, daily for ten days. Fatty changes were
taken as an index of hepatoxicity because other changes namely
fibrosis and cirrhosis cannot be produced in rats. Biochemical
and hispathological studies revealed that 50% alchoholic extract
of roots and leaves of P. niruri (PN), commonly known as Jaramala
in Hindi, has got hepatoprotective effect on alcohol induced
liver cell damage in non-hepatectomised and partially hepatetomised
rats. The root extract of PN was found to be more effective
hepatoprotective agent than the leaves extract. 50% of alcoholic
extract of leaves of Ricinus communis (RC) commonly known
as Arand in Hindi, did not shoe any significant hepatoprotective
activity.
- Study
of Phyllanthus product inhibition effect on mice
liver cancer.
Yang SL, Guang SH & Zhu YT. Journal of Cancer. 2000. Vol. 19(8)
837-838.
Study showed a Chinese medicine with Phyllanthus
as chief ingredient has an inhibition effect on mice transplanted
liver cancer. It showed better effect as compared to BCG.
Traditionally
uses
- A
survey of medicinal plants of Minas Gerais, Brazil
G. Schmeda Hirschmann and A. Rojas de Arias. Jour of Ethnopharm,
29, 1990, 159-172.
Historically, Phyllanthus infusion or decoction is
taken to treat renal diseases. It dissolves kidney and bladder
stones. The roots are used for jaundice.
- Amazonian
Ethnobotanical Dictionary
James Alan Duke and Rodolfo Vasquez, 1994, by CRC Press.
Phyllanthus
niruri is considered digestive, diuretic, emmenagogue,
laxative, stomachic, tonic and vermifuge. Has proven antihepatotoxic,
antispasmodic, antiviral, bactericidal, diuretic, febrifugal,
and hypoglycemic activity.
- Antihepatotoxic
principles of Phyllanthus niruri herbs.
Syamasundar KV, Singh B, Thakur RS, Husain A, Kiso Y, Hikino
H.
Among phyllanthin, hypophyllanthin, triacontanal and tricontanol
isolated from a hexane extract of Phyllanthus niruri,
phyllanthin and hypophyllanthin protected against carbon tetrachloride-
and galactosamine-induced cytotoxicity in primary cultured
rat hepatocytes, while triacontanal was protective only against
galactosamine-induced toxicity.
- Usage
and bioassays in Phyllanthus. IV. Clustering of
antiviral uses and other effects.
Unander DW, Webster GL, Blumberg BS. J Ethnopharmacol 1995 Jan;45(1):1-18
A number of species of the genus Phyllanthus have
been tested for their efficacy as antivirals, partly on the
basis of references to traditional usage for the treatment
of diseases possibly having a viral origin. Consideration
of the data from ethnobotany, in vitro assays and clinical
trials supported the presence of some type of biological activity
particularly within the subgenus Phyllanthus. Although
the herbaceous species of subgenus Phyllanthus have
been extensively used to treat jaundice, and have generally
inhibited hepadnavirus DNAP.
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