Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of -methylumbelliferone in human UGT isoforms

Molecules. 2010 May 14;15(5):3578-92.

Ismail S, Hanapi NA, Ab Halim MR, Uchaipichat V, Mackenzie PI.

Centre for Drug Research, Universiti Sains Malaysia, 11800, Penang,
Malaysia. sabaris@usm.my

The effects of Andrographis paniculata and Orthosiphon stamineus
extracts on the in vitro glucuronidation of 4-methylumbelliferone
(4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7,
UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential
inhibitory effects of both of the extracts on the activity of each of
the UGT isoforms were investigated using 4MU as the substrate.
Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor,
MgCl(2), cell lysate of respective isoform, and 4MU at the approximate
apparent K(m) or S(50) value of each isoform. Final concentrations of
Andrographis paniculata and Orthosiphon stamineus extracts used were
0.025, 0.25, 2.5, 25 and 50 microg/mL and 0.01, 0.10, 1.0, 10 and 50
microg/mL respectively. Both extracts variably inhibited the activity
of most of the isoforms in a concentration dependent manner.
Andrographis paniculata extract was the better inhibitor of all the
isoforms studied (IC(50) 1.70 microg/mL for UGT1A3, 2.57 microg/mL for
UGT1A8, 2.82 microg/mL for UGT2B7, 5.00 micorg/mL for UGT1A1, 5.66
microg/mL for UGT1A6, 9.88 microg/mL for UGT1A7 and 15.66 microg/mL
for UGT1A10). Both extracts showed less than 70% inhibition of
UGT2B15, so the IC(50) values were >50 microg/mL. The inhibition of
human UGTs by Andrographis paniculata and Orthosiphon stamineus
extracts in vitro suggests a potential for drug-herbal extract
interactions in the therapeutic setting.

PMID: 20657500 [PubMed - in process]

ED-XRF spectrometric analysis of comparative elemental composition of in vivo and in vitro roots of Andrographis paniculata (Burm.f.) Wall. ex Nees-a multi-medicinal herb

Appl Radiat Isot. 2010 Jun 25. [Epub ahead of print]

Behera PR, Nayak P, Barik DP, Rautray TR, Thirunavoukkarasu M, Chand PK.

Plant Cell and Tissue culture Facility, Post-Graduate Department of
Botany, Utkal University, Vani Vihar, Bhubaneswar 751004, Orissa,
India; Plant Biotechnology Lab, Institute of Minerals & Materials
Technology (CSIR), Bhubaneswar 751013, Orissa, India.

The multi-elemental composition of in vitro-proliferated root tissues
of Andrographis paniculata (Burm.f.) Wall. ex Nees was compared with
that of the naturally grown in vivo plants. Trace elements namely Cr,
Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr and Pb in addition to two
macro-elements K and Ca were identified and quantified in root tissues
of both sources using the energy dispersive X-ray fluorescence
(ED-XRF) technique. ED-XRF analysis was performed using Mo K X-rays
generated from a secondary molybdenum target. The elemental content of
in vitro roots was found to be at par with that of naturally grown
plants of the same species. This opens up a possibility of exploiting
in vitro root cultures as a viable, alternative and renewable source
of phytochemicals of relevance, besides providing a means for
conservation of the valuable natural resources. Copyright © 2010
Elsevier Ltd. All rights reserved.

PMID: 20637644 [PubMed - as supplied by publisher]

14-Deoxyandrographolide desensitizes hepatocytes to tumour necrosis factor-alpha-induced apoptosis through calcium-dependent tumour necrosis factor receptor superfamily member 1A release via the NO/cGMP pathway

Br J Pharmacol. 2010 Aug;160(7):1823-43.

Roy DN, Mandal S, Sen G, Mukhopadhyay S, Biswas T.

Cell Biology and Physiology Division, Indian Institute of Chemical
Biology, A Unit of Council of Scientific and Industrial Research,
Kolkata, India.

BACKGROUND AND PURPOSE Andrographis paniculata (AP) has been found to
display hepatoprotective effect, although the mechanism of action of
the active compounds of AP in this context still remains unclear.
Here, we evaluated the hepatoprotective efficacy of
14-deoxyandrographolide (14-DAG), a bioactive compound of AP,
particularly its role in desensitization of hepatocytes to tumour
necrosis factor-alpha (TNF-alpha)-induced signalling of apoptosis.
EXPERIMENTAL APPROACH TNF-alpha-mediated ligand receptor interaction
in hepatocytes in the presence of 14-DAG was studied in vitro in
primary hepatocyte cultures, with the help of co-immunoprecipitation,
confocal microscopy and FACS analysis. Events associated with
14-DAG-induced TNFRSF1A release from hepatocytes were determined using
immunoblotting, biochemical assay and fluorimetric studies.
Pulse-chase experiments with radiolabelled TNF-alpha and detection of
apoptotic nuclei by terminal transferase-mediated dUTP nick-end
labelling were performed under in vivo conditions. KEY RESULTS 14-DAG
down-regulated the formation of death-inducing signalling complex,
resulting in desensitization of hepatocytes to TNF-alpha-induced
apoptosis. Pretreatment of hepatocytes with 14-DAG accentuated
microsomal Ca-ATPase activity through induction of NO/cGMP pathway.
This resulted in enhanced calcium influx into microsomal lumen with
the formation of TNFRSF1A-ARTS-1-NUCB2 complex in cellular vesicles.
It was followed by the release of full-length 55 kDa TNFRSF1A and a
reduction in the number of cell surface TNFRSF1A, which eventually
caused diminution of TNF-alpha signal in hepatocytes. CONCLUSION AND
IMPLICATION Taken together, the results demonstrate for the first time
that 14-DAG desensitizes hepatocytes to TNF-alpha-mediated apoptosis
through the release of TNFRSF1A. This can be used as a strategy
against cytokine-mediated hepatocyte apoptosis in liver dysfunctions.

PMID: 20649583 [PubMed - in process]