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Anti-inflammatory and preventive activity of white mulberry root bark extract in an experimental model of pancreatitis


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Pancreatitis is characterized by highly morbid inflammation in the pancreas. Currently, there is no specific drug available for pancreatitis except supportive medicines. The present study assessed the pancreato-protective effect of Morus alba root bark extract by using alcohol and cerulein-induced model of pancreatitis. The study also investigated the phytochemical profile through GC-MS and HPLC. Methanolic extract of Morus alba root bark extract (MEMARB) was subjected to GC-MS and HPLC studies. Male albino Wistar rats were administered ethanol (0%-36%) and cerulein (20 μg/kg b.wt. i.p.) with or without MEMARB. Serum lipase, amylase, caspase-1, lipid peroxidation products, glutathione and enzymatic antioxidants were determined. Histological changes in the pancreas were assessed. Cudraflavone B in MEMARB was quantified by HPLC. Significant amount of Cudraflavone B was detected by quantitative HPLC. Marked increase in the levels of serum amylase, lipase, caspase-1, IL-18 and IL-1β were observed in ethanol and cerulein administered rats than in MEMARB co-administered rats. In MEMARB co-administered rats, the antioxidant status was restored to near normal levels. Histological examinations showed that MEMARB significantly reduced the inflammatory and fibrotic changes. The results reveal the potent pancreato-protective effects of Morus alba root bark. The anti-inflammatory effect of Morus alba root bark extract might be due to the presence of various phytonutrients including Cudraflavone B. © 2018 Center for Food and Biomolecules, National Taiwan University.
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Anti-inammatory and preventive activity of white mulberry root
bark extract in an experimental model of pancreatitis
Kavitha Yuvaraj, Geetha Arumugam
Department of Biochemistry, Bharathi Women's College, Broadway, Chennai, 600 108, India
article info
Article history:
Received 13 May 2017
Received in revised form
18 January 2018
Accepted 19 January 2018
Available online 2 March 2018
Cudraavone B
Morus alba
Pancreatitis is characterized by highly morbid inammation in the pancreas. Currently, there is no
specic drug available for pancreatitis except supportive medicines. The present study assessed the
pancreato-protective effect of Morus alba root bark extract by using alcohol and cerulein-induced model
of pancreatitis. The study also investigated the phytochemical prole through GC-MS and HPLC. Meth-
anolic extract of Morus alba root bark extract (MEMARB) was subjected to GC-MS and HPLC studies. Male
albino Wistar rats were administered ethanol (0%e36%) and cerulein (20
g/kg b.wt. i.p.) with or without
MEMARB. Serum lipase, amylase, caspase-1, lipid peroxidation products, glutathione and enzymatic
antioxidants were determined. Histological changes in the pancreas were assessed. Cudraavone B in
MEMARB was quantied by HPLC. Signicant amount of Cudraavone B was detected by quantitative
HPLC. Marked increase in the levels of serum amylase, lipase, caspase-1, IL-18 and IL-1
were observed in
ethanol and cerulein administered rats than in MEMARB co-administered rats. In MEMARB co-
administered rats, the antioxidant status was restored to near normal levels. Histological examinations
showed that MEMARB signicantly reduced the inammatory and brotic changes. The results reveal the
potent pancreato-protective effects of Morus alba root bark. The anti-inammatory effect of Morus alba
root bark extract might be due to the presence of various phytonutrients including Cudraavone B.
©2018 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier
Taiwan LLC. This is an open access article under the CC BY-NC-ND license (
1. Introduction
Pancreatitis is an inammatory response initiated in the
pancreatic parenchyma due to acinar cell injury. The underlying
pathomechanism is the premature ectopic activation of the master
proteolytic zymogen trypsinogen, to active trypsin, precipitating a
cascade of zymogen activation and auto digestionof the pancreas.
Persistent, irreversible inammation and brosis of the
pancreas are characteristics of chronic pancreatitis (CP). Symptoms
of CP include abdominal pain, frequent acute pancreatitis (AP)
episodes, exocrine and endocrine insufciency.
Alcohol abuse
causes 70% of CP while smoking, gene mutations, hyperparathy-
roidism and autoimmunity are other etiologies.
Chronic pancrea-
titis has a worldwide prevalence of 50/100,000 persons. Tropical
calcic pancreatitis (TCP), a rare form of CP, has a prevalence of
20e125/100,000 persons in southern India. 5% of CP patients and
40e50% of hereditary pancreatitis patients develop highly lethal
pancreatic cancer.
Current management guidelines recommend only supportive
measures like hospitalization, intensive uid resuscitation, bowel
rest, parenteral nutrition, enzyme supplements and pain manage-
ment through non-steroidal anti-inammatory drugs (NSAIDs).
In both acute and chronic pancreatitis injured and dying
pancreatic acinar cells are the primary drivers of inammation and
initiators of necroptosis and pyroptosis, key determinants of dis-
ease severity. Acinar cells elaborate immune responses by secreting
cytokines (TNF-
, IL-1
, IL-6, and IL-10), chemokines (MCP-1) and
endogenous damage associated molecular patterns (DAMPs).
NLRP3 inammasome is a multiprotein intracellular innate
immune sensor consisting of NLRP3, apoptosis-associated speck-
like protein (ASC) and procaspase-1. It assembles in response to
Abbreviations: AP, acute pancreatitis; CP, chronic pancreatitis; TCP, tropical
calcic pancreatitis; MCP 1, monocyte chemotactic protein 1; DAMPS, damage
associated molecular patterns; PSC, pancreatic stellate cell; NF-kappa B, nuclear
factor kappa-light-chain-enhancer of activated B cells; AP1, activator protein 1;
MEMARB, methanolic extract of Morus alba root bark.
*Corresponding author.
E-mail address: (A. Geetha).
Peer review under responsibility of The Center for Food and Biomolecules,
National Taiwan University.
Contents lists available at ScienceDirect
Journal of Traditional and Complementary Medicine
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Journal of Traditional and Complementary Medicine 8 (2018) 497e505
diverse stimuli and forms the scaffold for the activation of pro-
inammatory cytokines IL-1beta and IL-18 and induces the
release of HMGB1 expression important in pancreatic inamma-
tion, parenchymal cell injury and disease resolution. Pro-
inammatory cytokines IL-1 beta and IL-18 are triggers of pyrop-
tosis, a highly lytic form of cell death, which appears to be pre-
dominant in pancreatitis.
In the face of a threat from rising pancreatitis cases and the
absence of a specic licensed drug, inammatory pathways have
been under scrutiny to nd suitable targets for potential anti-
inammatory drug molecules. Various anti-inammatory effec-
tors that have been tested include thalidomide (targets TNF-alpha),
panhaematin (decreases leukocyte inltration), IL-R antagonist
montelukast, MCP 1 inhibitors, COX- 2 inhibitor avocoxid, vitamin
K3 (inhibits autophagy) and the broad anti-inammatory effects of
agents like quercetin, resveratrol and curcumin.
Morus alba L. or white mulberry is native to northern China and
has been naturalized and cultivated throughout Asia and Europe. It
has long-standing ethno medicinal signicance. Various parts of
the plant have been used in traditional Asian medicine. Phyto-
chemical analyses have identied alkaloids, avonoids, avones,
avanones, stilbenes, benzophenones, coumarin derivatives and
terpenoids in the root bark of M. alba
. Morus is one of the few
genera to contain prenylated avonoids. Prenyl avonoids are
credited with enhanced biological effects attributed to the prenyl
But, their scientic validation should be taken care of.
The bioactive principles from Morus alba root bark are reported
to have antibacterial, antiviral, antioxidant, hypoglycemic, neuro-
protective, nephroprotective, antiulcer, analgesic and anti-
inammatory properties.
The aim of the present investigation is to assess the therapeutic
efcacy of phytonutrients of white mulberry roots with special
reference to their inuence on the level of cytokine production and
their impact on acinar cell damage monitored in terms of serum
and pancreatic marker enzymes and cellular antioxidants.
2. Materials and methods
2.1. Chemicals
Reference standards for HPLC - gallic acid, galangin, rutin,
quercetin and thymoquinone - were obtained from LGC Pro-
mochem India Pvt. Ltd., (Bangalore, India). HPLC grade solvents
were purchased from Merck India. ELISA kit for IL-I
was purchased
from Abcam and Invitrogen ELISA kit for IL-18 was purchased from
Thermo Fisher Scientic. Lipase and alpha-amylase assay kits were
procured from Coral Clinical Systems, Goa, India. All other chem-
icals used were of analytical grade.
2.2. Plant material collection, identication and extraction
Fresh Morus alba roots were collected from the Plant Sciences
department, University of Madras, Guindy Campus, Chennai,
department of Sericulture, Vitchanthangal, Kancheepuram District,
Tamil Nadu and a private mulberry farm at Purisai, Kancheepuram
District, Tamil Nadu. The plant material was authenticated by
Professor P. Jayaraman, Director, Plant Anatomy Research Centre,
West Tambaram, Chennai. The herbarium specimen (PARC/2015/
3144) was preserved for future reference in the Department of
Biochemistry, Bharathi Women's College. The roots were pooled,
cleaned under tap water and air-dried for 2e3 weeks. Completely
dry roots were lightly scraped to reveal the yellowish layer un-
derneath. The root bark or cortex was peeled off with the help of a
knife, cut into small pieces and powdered in a blender. The crude
powder was sieved to obtain a ne homogenous powder. M.alba
root bark powder was soaked in methanol and left to agitate on a
shaker for 24hrs. The extract was ltered. The residue was extrac-
ted again with fresh methanol to ensure complete extraction. The
ltrates were air dried to a powder, sieved and stored in an air-tight
container at 4
C. For animal experimentation, a homogenous sus-
pension of the bark powder was prepared with 0.1% DMSO.
2.3. Animals
Adult male albino Wistar rats (175e200g, seven-eight weeks
old) used for the study were housed under hygienic conditions [22-
C] in polypropylene cages under 12 h light/12 h dark cycle. The
animals were allowed free access to water and standard pelleted rat
chow during the acclimatization period. Animal maintenance and
experimentation protocols conformed to the guidelines of the
Institutional Animal Ethics Committee constituted by the Com-
mittee for the Purpose of Control and Supervision of Experiments
on Animal (CPCSEA), Government of India, [XVII/VELS/PCOL/02/
2.4. Experimental protocols
2.4.1. Preliminary phytochemical screening by GC-MS
The methanolic extract of the root bark of white mulberry
(M.alba) was subjected to GC-MS analysis. The analysis was carried
out on Agilent 6890N gas chromatograph with HP-5ms column
coupled to a mass spectrometer JEOL GC-MATE II in the electron
ionization (EI) mode with ionization voltage set to 70eV. The mass
spectral scan range of the mass analyser was set to 50e600 amu.
Helium was used as a carrier gas at a constant ow of 1 mL/min. The
front inlet temperature was 220
C. The GC-oven was set for the
following temperature prole: ramp rate from 50
C/min. NIST (National Institute of Standards and Technology)
GC-MS mass spectral database was used to interpret the mass
spectrum using the retention time.
2.4.2. HPLC for identication of avonoids and quantication of
Cudraavone B
Accurately weighed quantities of the standards and the sample
were transferred to separate volumetric asks and dissolved in
methanol and diluted to a specic concentration. A specic quan-
tity of Morus alba root bark powder was reuxed with extraction
solvent (methanol: water: hydrochloric acid) for 135 min to
hydrolyse the avonoid glycosides and contents were made up
with methanol. An equal volume of the standard and sample
L) was then used for the HPLC analysis on Shimadzu (Japan),
HPLC Class VP series with a UVevis detector. The samples were run
on a C18 column (100 Åpore size, 3.5
m, 4.6 mm 250 mm)
40 min run time. The mobile phase used was a mixture of meth-
anol, water and phosphoric acid mixed in the ratio (100:100:1). The
elution was isocratic with the ow rate set at 1.5 mL/min. The a-
vonoids were monitored by the ultraviolet detector set at 270 nm.
EZChrom Data System was used for data acquisition, processing and
report generation.The resulting chromatograms were recorded
and the areas under the major peaks measured. Flavonoids were
identied by matching the retention time and their spectral char-
acteristics against those of the standards.
2.4.3. Ethanol and cerulein-induced chronic pancreatitis
After one-week of acclimatization, the animals were randomly
divided into four groups of six animals each. Group 1: received
normal diet (standard rat chow) for 5 weeks; Group 2: received the
normal diet and MEMARB (300 mg/kg body weight/day) orally for
the last 3 weeks of the experimental period; Group 3: received an
ethanol containing isocaloric diet, and 20
g/kg body weight of
Y. Kavitha, A. Geetha / Journal of Traditional and Complementary Medicine 8 (2018) 497e505498
cerulein intraperitoneally for the last 3 weeks Group 4: received an
ethanol containing isocaloric diet, 20
g/kg body weight of cerulein
intraperitoneally and MEMARB (300 mg/kg body weight) orally, for
the last 3 weeks.
At the end of the experimental period, rats were fasted over-
night and anesthetized by intramuscular injection of ketamine
hydrochloride [30 mg/kg body wt.] and killed by cervical decapi-
tation. Blood was collected and the serum separated was stored
appropriately until further analyses.
2.4.4. Tissue homogenate preparation
Pancreas was removed carefully, washed and homogenized in
0.1M Tris-HCl buffer pH 7.4 and centrifuged at low speed to remove
all the cell debris. The supernatant was used for the determination
of caspase-1, and antioxidant enzymes such as superoxide dis-
mutase (SOD), catalase (CAT) and glutathione peroxidase (GP
estimation of reduced glutathione (GSH) and estimation of lipid
2.4.5. Biochemical investigations Assay of IL-1
.IL-1 beta rat sandwich ELISA Kit (AB100767)
was purchased and the assay was performed conforming to man-
ufacturer's instructions. Assay of IL-18. The IL-18 Rat ELISA Kit (KRC2341) was used
to quantify serum IL-18. Instructions provided in the kit manual
were followed. Assay of caspase-1. For the colorimetric assay of caspase-1
activity in serum and pancreatic homogenate, the method of
was adopted. The pancreas was homogenised in a
lysis buffer (25 mM HEPES pH 7.5), 1mM EDTA, 10
g of aprotinin/
mL, 10
g of leupeptin/mL, 2 mM dithiothreitol at 5mL/100 mg of
pancreas tissue. Extracts were centrifuged at 15,000 g for 30 min at
C. The supernatant was recentrifuged at 200,000 g for 1 hat 4
and the supernatant used for the measurement of capase-1 activity.
The assay is based on the spectrophotometric detection of the
chromophore p-nitroanilide (pNA), released from the labelled
substrate YVAD-pNA by caspase-1, at 400 or 405 nm. Activity was
expressed as pg/mL serum and pM/mg protein. Assay of myeloperoxidase. The supernatants of cell free
extracts were assayed for MPO as described by Bradley et al.
Briey, the rate at which a coloured product formed during the
MPO dependent reaction with o-dianisidine dihydrochloride
(0.167 mg/mL) was measured kinetically at 460 nm and the activity
was expressed as units/mg protein. Assay of serum lipase and serum alpha-amylase.
Serum lipase and serum alpha-amylase levels were determined by
turbidimetry and colorimetry respectively, following instructions
provided in the kit manual. Estimation of lipid peroxides. Thiobarbituric acid reactive
substances (TBARS) assay was performed to determine level of
malondialdehyde in the pancreas according to the protocol of
Draper and Hadley.
Briey, the reaction mix which consisted of
0.5 mL pancreatic homogenate, 10% PTA and TBA was incubated in a
boiling water bath, cooled and centrifuged. Absorbance of the pink
chromogen formed was measured at 540 nm to determine the level
of malondialdehyde formation which was expressed as nM/100 mg
tissue protein. Estimation of 4-HNE (4-hydroxynonenal) in the
pancreas was done following the method of Kinter et al.
where, 4-
HNE in the sample was derivatized with dinitrophenyl hydrazine
(DNPH). The product formed was extracted 3 times with hexane,
evaporated to dryness and solubilized with methanol prior to
measurement of absorbance at 350 nm. Levels of 4-HNE in the
samples was expressed as
M/mg tissue protein. Estimation of reduced glutathione and antioxidant enzymes.
GSH level in the pancreas was measured following the protocol of
Moron et al.
DTNB was added to the pancreatic homogenate and
the yellow complex formed was estimated spectrophotometrically
at 412nm and the level was expressed as mg/gm tissue protein.
Glutathione peroxidase (GPx) was assayed according to the method
of Floh
e and Günzler
where a specic volume of the enzyme
preparation was allowed to react with H
for a specied time
period and the remaining GSH was estimated by Ellman's reaction.
Activity expressed as nM of glutathione oxidized/min/mg protein.
Superoxide dismutase (SOD) activity was measured according to
the protocol of Kakker et al.
The inhibition of reduction of nitro-
blue tetrazolium (NBT) to blue coloured formazan in the presence
of phenazine methosulfate (PMS) and NADH was measured at
560 nm using n-butanol as blank. Following the method of Sinha
et al.,
catalase activity was measured as the amount of enzyme
required to decompose hydrogen peroxide in the presence of di-
chromate and acetic acid. Absorbance of chromic acetate formed
was measured at 620 nm. The enzyme activity was expressed as
of H
consumed/min/mg protein. Estimation of protein. Bradford method
was used to
determine the protein concentration in the tissue homogenate. The
protein level was used to calculate the enzyme activity in tissue
2.4.6. Histological assessment
Freshly dissected pancreas was washed with ice-cold 0.9% saline
and xed in 10% formo-saline for 24 h. The tissue specimens were
dehydrated with alcohol, cleaned with methyl benzoate and
embedded in parafn wax. Sections in cryostat from snap frozen
tissues were cut into 5
M thickness and stained with haematox-
ylin and eosin for microscopic evaluation.
2.4.7. Statistical analyses
The statistics software package (SPSS for Windows V.10) was
used for the data analyses. The statistical signicance of mean
values between different groups was determined by applying one
way ANOVA with post hoc Bonferroni test and the P value <0.05
was considered as signicant.
3. Results
3.1. Phytochemical screening by GC-MS
GC-MS analysis revealed the presence of the following com-
pounds: 2H-1-Benzopyran-2-one (Coumarin), Eugenol, 5,7-
dihydroxyavone (Chrysin), 5,7-dihydroxyisoavone (Mefenamic
acid), 4
5,7-Trihydroxy isoavone (Genistein), 4-H1-Benzopyran-4-
one, 5,7-dihydroxy-2-(4-hydroxyphenyl)- (Apigenin), 4
5,7-dihydroxy isoavone (Biochanin A), Psi-baptigenin, Rhein,
Morin, 5,7-dimethoxy avone, Vitamin E, 8-glycosyl apigenin
(Vitexin). Table 1 lists out their retention times and bioactivities.
Fig. 1 shows the GC-MS chromatogram of MEMARB.
3.2. Phytochemical analysis of MEMARB by HPLC-UV analysis
Fig. 2 displays the HPLC-UV chromatograms. HPLC-UV chro-
matogram of MEMARB generated two peaks at 270 nm with
retention times 3.19 and 8.53 min (Fig. 2C). The peaks were iden-
tied to be Cudraavone B (0.9 mg/gm; RT 3.19 min) and Quercetin
Y. Kavitha, A. Geetha / Journal of Traditional and Complementary Medicine 8 (2018) 497e505 499
(0.1 mg/gm; RT 8.53 min), by matching the retention times with
those of the reference standards run under the same conditions
(Fig. 2A and B).
3.3. Effect of MEMARB on the levels of serum lipase and serum
Table 2 shows the levels of serum lipase and serum alpha-
amylase in the experimental groups. Rats administered ethanol
and cerulein showed signicant elevation in the levels of serum
lipase and serum amylase when compared to the normal control
animals (p <0.05). Serum levels of these markers of pancreatic
injury reversed towards normal values in MEMARB treated rats
(p <0.05). Rats fed normal diet and MEMARB showed normal levels
of the enzymes.
3.4. Effect of MEMARB on serum and tissue inammatory markers
Table 3 charts out the activity levels of MPO and caspase-1 in the
pancreas and the levels of caspase-1, IL-1beta, and IL-18 in the
serum of the experimental animals. Notable increase in the levels of
these inammatory markers was observed in the ethanol and
cerulein administered rats when compared to rats co-administered
MEMARB. A non-signicant reduction of the inammatory markers
was seen in the MEMARB control group.
Table 1
List of compounds identied in the methanolic extract of Morus alba root bark by GC-MS.
No. RT
Name of the compound Molecular
Molecular Weight
1 12.1 2H-1-Benzopyran-2-one (Coumarin) C
146.14 Venotonic
2 14.5 Eugenol C
164.2 Improves cell-mediated immunity, local antiseptic
3 15.72 Chrysin C
254.24 Antiinammatory, antioxidative, anti-hypercholesterolemic
4 15.72 5,7-dihydroxyisoavone (Mefenamic acid) C
254.23 Anti-inammatory, inhibitor of prostaglandin synthesis,
5 16.75 4
,5,7-Trihydroxy isoavone (Genistein) C
270.24 Anti-angiogenic, vasculoprotective
6 17.1 Apigenin C
270.4 Anti-inammatory, anti-proliferative, anti-metastatic
7 17.57 Biochanin A C
284.27 Anti-inammatory,antidiabetic, anticarcinogenic, lipid
metabolism regulator
8 17.57 Pseudobaptigenin C
282.24 Nutrient isoavone
9 17.75 Rhein (Cassic acid) C
284.22 Anti-microbial, antibiotic, apoptotic, antiproliferative
10 18.55 Morin C
302.24 Anti-inammatory, antihypertensive, anti-angiogenic,
hepatoprotective, neuroprotective
11 18.8 5,7-dimethoxy avone C
282.29 Anti-proliferative, apoptotic
12 19.7 Vitamin E C
430.71 Anti-oxidant
13 20.63 1,6-Heptadiene-3,5 dione,1,7-bis(4-hydroxy-3-methoxy
368.38 Anti-inammatory, anti-oxidant, antimicrobial, anticancer
14 20.67 Vitexin C
432.38 Anti-inammatory, anti-cancer, neuroprotective
Human Metabolome Database (Ref).
Fig. 1. Total Ion Chromatogram generated from the GC-MS analysis of the methanolic extract of Morus alba root bark: 1) 2H-1-Benzopyran-2-one (Coumarin) 2) Eugenol 3) 5,7-
dihydroxyavone (Chrysin) 4) 5,7-dihydroxyisoavone (Mefenamic acid) 5) 405,7-Trihydroxy isoavone (Genistein) 6) 4-H1-Benzopyran-4-one, 5,7-dihydroxy-2-(4-
hydroxyphenyl)- (Apigenin) 7) 40-methoxy-5,7-dihydroxy isoavone (Biochanin A) 8) Psi-baptigenin 9) Rhein 10) Morin 11) 5,7-dimethoxy avone 12) Vitamin E 13) 8-glycosyl
apigenin (Vitexin).
Y. Kavitha, A. Geetha / Journal of Traditional and Complementary Medicine 8 (2018) 497e505500
3.5. Effect of MEMARB on the redox status elevels of TBARS, 4-HNE
and reduced glutathione (GSH)
Table 4 displays the levels of lipid peroxidation products and the
level of the antioxidant glutathione in the pancreatic tissue. In-
crease in the levels of lipid peroxidation products were found to be
highly signicant in the ethanol and cerulein administered exper-
imental group while the level of the molecular antioxidant GSH was
found to be decreased, when compared to the normal rats. MEM-
ARB administration markedly reduced the levels of TBARS and 4-
HNE and increased levels of GSH. Levels of TBARS, 4-HNE and
GSH showed no signicant change in MEMARB control rats.
3.6. Effect of MEMARB on the redox status eactivity levels of
antioxidant enzymes
Activity levels of the antioxidant enzymes, GPx, SOD and cata-
lase are shown in Table 5. In the ethanol and cerulein-induced
pancreatitis group, levels of GPx, SOD and catalase were signi-
cantly depleted relative to the normal control group. No signicant
changes were observed in the MEMARB control animals. In the
Fig. 2. High Performance Liquid Chromatography (HPLC) chromatograph of (A) reference standards; (B) Cudraavone B standard; (C) MEMARB. Conditions: Mobile phase:
methanol: acetic acid: water (100:100:1); ow rate: 1.5 ml/min; Run time: 40 min. Wavelength: 270 nm.
Table 2
Effect of MEMARB on the levels of serum lipase and serum alpha-amylase.
Group Lipase (IU/L) Amylase (IU/L)
Normal Control 182 ±19 2732.21 ±360.65
MEMARB Control 156 ±16
2614.02 ±316.3
EtOH þCerulein 425 ±50* 4772.47 ±629.97*
EtOH þCerulein þMEMARB 236 ±31* 3198.78 ±422.24*
Data were analysed by one-way ANOVA followed by post-hoc Bonferroni test.
Values are expressed as mean ±S.D. of 6 rats in each group. Statistical signicance
was calculated by comparing normal control vs. MEMARB control; Control vs.
EtOH þCerulein; EtOH þCerulein vs. EtOH þCerulein þMEMARB. *p ¼0.000; NS
Y. Kavitha, A. Geetha / Journal of Traditional and Complementary Medicine 8 (2018) 497e505 501
experimental group co-administered with MEMARB, the levels of
the antioxidant enzymes were restored.
3.7. Effect of MEMARB on the histology of the pancreatic and liver
Fig. 3 and Fig. 4 show photomicrographs of hematoxylin and
eosin stained sections (400X) of the pancreas and the liver
respectively. Pancreatic and liver sections from normal control and
MEMARB control rats showed normal tissue architecture (Fig. 3 (a,
c); Fig. 4 (a, c)). Section of the pancreas from the ethanol and cer-
ulein administered group showed neutrophil inltration and
brotic changes (Fig. 3 (c)) and the liver section from the same
group showed tissue inltration of neutrophils (Fig. 4c). Tissue ar-
chitecture of the pancreas (Fig. 3d) and the liver (Fig. 4d) was found
to be restored to normal in MEMARB treated experimental group.
4. Discussion
In this investigation, the anti-inammatory and antioxidant
capacity of MEMARB was evaluated in vivo in the best-
characterised ethanol and cerulein-induced rat model of experi-
mental pancreatitis.
Supramaximal doses of cerulein, an analogue of the physiolog-
ical secretagogue cholecystokinin, stimulates protein-rich pancre-
atic secretions and disturbs the actin cytoskeleton and vesicular
transport, thereby suppressing the export of digestive enzymes.
This precipitates premature zymogen activation within the acinar
cells with subsequent tissue injury and pathology similar to human
pancreatitis. Ethanol when co-administered potentiates the effect
of cerulein.
Ethanol is the principal etiological factor for acute and
Table 3
Effect of MEMARB on serum and tissue inammatory markers.
Group Caspase-1 MPO IL-1beta IL-18
Serum (pg/ml) Pancreas (pM/mg protein) Pancreas (Units/mg protein) Serum pg/ml Serum pg/ml
Normal Control 12.6 ±1.8 12.6 ±1.5 2.16 ±0.4 15.5 ±2.6 200.5 ±30.1
MEMARB Control 11.5 ±1.3
10.3 ±1.2
1.82 ±0.2
13.6 ±2.1
170 ±21.6
EtOH þCerulein 21.5 ±2.8* 49.6 ±5.2* 3.98 ±0.4* 31.5 ±4.5* 360.5 ±42*
EtOH þCerulein þMEMARB 14.3 ±1.8* 20.5 ±2.8* 2.56 ±0.3* 20.5 ±3.1* 240 ±32*
Data were analysed by one-way ANOVA followed by post-hoc Bonferroni test. Values are expressed as mean ±S.D. of 6 rats in each group. Statistical signicance was calculated
by comparing normal control vs. MEMARB control; Control vs. EtOH þCerulein; EtOH þCerulein vs. EtOH þCerulein þMEMARB. *p ¼0.000; NS non-signicant.
Table 4
Effect of MEMARB on the redox status elevels of TBARS, 4-HNE and reduced glutathione (GSH).
Group TBARS (nM/100 mg protein) 4-HNE (
M/g protein) GSH (mg/g protein)
Pancreas Pancreas Pancreas
Normal Control 1776.00 ±225.55 2.000 ±0.24 96.015±11.62
MEMARB Control 1782.40 ±190.72
2.13 ±0.21
98.82 ±12.06
EtOH þCerulein 3408.12 ±415.8* 8.100 ±0.96* 49.600 ±6.00*
EtOH þCerulein þMEMARB 1806.66 ±229.44* 5.062 ±0.60* 93.330 ±11.29*
Data were analysed by one-way ANOVA followed by post-hoc Bonferroni test. Values are expressed as mean ±S.D. of 6 rats in each group. Statistical signicance was calculated
by comparing normal control vs. MEMARB control; Control vs. EtOH þCerulein; EtOH þCerulein vs. EtOH þCerulein þMEMARB. *p ¼0.000; NS non-signicant.
Table 5
Effect of MEMARB on the redox status - Activity levels of antioxidant enzymes.
Group GPx (nM GSH consumed/min/mg protein) SOD (U/mg protein) Catalase (U/mg protein)
Pancreas Pancreas Pancreas
Normal Control 324.5 ±42.5 14.2 ±1.49 114.4 ±15.90
MEMARB Control 339.2 ±40.02
14.5 ±1.65
112.1 ±16.37
EtOH þCerulein 233.6 ±29.43* 8.2 ±0.97* 72.8 ±7.79*
EtOH þCerulein þMEMARB 353.33 ±46.29* 11.7 ±1.51* 106.3 ±12.65*
Data were analysed by one-way ANOVA followed by post-hoc Bonferroni test. Values are expressed as mean ±S.D. of 6 rats in each group. Statistical signicance was calculated
by comparing normal control vs. MEMARB control; Control vs. EtOH þCerulein; EtOH þCerulein vs. EtOH þCerulein þMEMARB. *p ¼0.000; NS non-signicant.
Fig. 3. Histology of the pancreas (H&E stain, 40 0X): (a) &(b) Photomicrograph of
pancreas from normal control and MEMARB control rats with intact acini and islets. (c)
Photomicrograph of pancreas from ethanol and cerulein administered rats showing
neutrophil inltration and brosis. (d) Photomicrograph of pancreas from MEMARB
co-administered rats showed restored tissue architecture. H&E: Haematoxylin &Eosin;
AC: acini; IS: islet; IL &F: inammation and brosis.
Y. Kavitha, A. Geetha / Journal of Traditional and Complementary Medicine 8 (2018) 497e505502
chronic pancreatitis with multifarious effects on the pancreas.
Pancreas metabolizes ethanol via oxidative and non-oxidative
pathways generating the toxic by-products, acetaldehyde and
fatty acid ethyl esters (FAEE), respectively. Acetaldehyde activates
pancreatic stellate cells (PSCs) promoting brosis while both
ethanol and acetaldehyde regulate transcription factors NF-kappaB
and AP1. FAEEs promote accumulation of cholesteryl esters leading
to lysosomal membrane fragility, destabilization of zymogen
granule membranes and cause a sustained increase in intra acinar
calcium levels. Recent research also indicates that ethanol in-
uences cholinergic pathways and CFTR channels in the pancreatic
ductal epithelium.
Presently, there being no specic and effective medication to
treat highly morbid pancreatic inammation, it becomes necessary
to seek potential therapeutic agents. The diverse array of secondary
metabolites present in plants has become the focus of research on
inammation. According to recent reports, apart from their anti-
oxidant properties, polyphenols including avonoids have been
found to have far-reaching modulatory effects on key mitochon-
drial pathways thus protecting the cell from the toxic effects of
xenobiotics and ROS.
Root bark of Morus alba, a highly valued traditional Chinese
medicine, is rich in Diels-Alder type adducts, stilbenes, alkaloids
and avonoids.
Prenylated avonoids, a sub-class of avonoids
abundant in Morus spp., have a lipophilic prenyl side-chain attached
to the avonoid skeleton. Prenylation is said to confer avonoids
with improved bioactivities.
Morus alba root bark has been shown
to have signicant antioxidant, anti-inammatory and anti-cancer
Cudraavone B, a prenylated avone from the root
bark of Morus alba is credited with potent anti-inammatory
properties. Current literature indicates that Morus alba root bark
is a rich source of this bioactive principle which could be a potential
anti-inammatory drug lead.
GC-MS is the method of choice for the screening of plant
bioactive constituents. GC-MS results showed the presence of a
variety of phytonutrients (Fig. 1;Table 1). HPLC-UV methods are
widely used to identify and quantify prenyl avonoids in biological
samples. Cudraavone B is reported to be a major prenyl avonoid
bioactive in M.alba root bark, with impressive anti-inammatory
HPLC-UV analysis of MEMARB (Fig. 2) conrmed the
presence of a signicant quantity of this compound in the sample
and could be responsible for its anti-inammatory properties. HPLC
analysis also revealed the presence quercetin, a potent anti-
inammatory, anti-oxidant and immunomodulatory avonoid.
Signicant increase in the serum levels of the digestive en-
zymes, lipase and pancreatic alpha-amylase is seen in pancreatic
Serum lipase and pancreatic alpha-amylase levels were
measured to assess the extent of injury to the pancreatic tissue
caused by EtOH and cerulein administration and the pancreato-
protective effect of MEMARB. Both serum lipase and pancreatic
alpha-amylase levels were found to be increased in EtOH and cer-
ulein administered animals. The amount of these enzymes was
restored to levels close to normal physiological levels in MEMARB
treated rats underlining the pancreato-protective potency of
Inammatory pathways underpin the basic pathology of
pancreatitis. Sterile inammation in pancreatitis leads to the acti-
vation of NLRP3 inammasome components caspase e1 and its
effectors- IL-1beta, and IL-18, the key determinants of the extent of
Serum levels of caspase-1 and the pro-inammatory
cytokines, IL-1beta and IL-18 are determined to evaluate the
progress of inammation. Levels of the pro-inammatory cytokines
and caspase-1 were found to be higher than normal in pancreatitis-
induced rats. MEMARB co-administered rats showed near-normal
levels of these markers of inammation adding further evidence
to the anti-inammatory property of MEMARB. Oxyresveratrol,
another major bioactive in white mulberry root bark, has been
shown to modulate inammatory responses by inhibiting MEK/ERK
pathway that leads to the activation of pro-inammatory cyto-
So, along with cudraavone B, oxyresveratrol could syn-
ergistically contribute to the anti-inammatory nature of Morus
alba. Oxyresveratrol from Morus bombycis, a Japanese mulberry, has
been experimentally proven to attenuate NLRP3 activation which
could be linked to its anti-inammatory potential
and could ac-
count for the NLRP3 attenuating effect of MEMARB.
Neutrophil inltration is a prominent feature of inammation in
any tissue. Acinar cell injury leads to the release of cytokines that
recruits neutrophils. Myeloperoxidase is expressed primarily by the
phagocytic neutrophil granulocytes. It generates the powerful
oxidant HOCl from H
and Cl
with bactericidal properties.
Myeloperoxidase activity is measured to assess the extent of
neutrophil inltration in pancreatic tissue.
Our results show sig-
nicant elevation in MPO activity in the pancreas of EtOH and
cerulein administered rats which could mirror pancreatic tissue
inammation induced by these molecules. This increase in in-
ammatory activity is countered in MEMARB co-administered an-
imals as evidenced by a fall in MPO activity in the pancreas.
MEMARB bio constituents and cudraavone B could be implicated
in this anti-inammatory effect.
Reactive oxygen and reactive nitrogen species (ROS/RNS) play
key roles in the pathogenesis of acute and chronic pancreatitis.
Pancreatic acinar cells contain phase I cytochrome P450 (CYP 450)
enzymes and phase II conjugation proteins for the metabolism of
xenobiotics. Oxidative stress may result from xenobiotic overload,
including alcohol, tobacco smoke, dietary toxins etc., and the
increased activity of these enzymes, leading to overwhelming in-
crease in ROS. Free radicals may deplete the endogenous antioxi-
dant molecules (mainly GSH) and the major antioxidant enzymes,
glutathione peroxidase (GP
), Superoxide dismutase (SOD) and
catalase and may also lead to an increase in the peroxidation of
cellular components, mainly unsaturated lipids. In this study, the
redox status of pancreatic tissue in diseased rats versus the
MEMARB-treated rats was determined by measuring the levels of
Fig. 4. Histology of the liver (H&E stain, 400X): (a) &(b) Photomicrograph of liver from
normal control and MEMARB control rats with normal tissue structure (c) Photomi-
crograph of liver from ethanol and cerulein administered rats showing neutrophil
inltration (d) Photomicrograph of liver from MEMARB co-administered rats with
reduced inammatory cell inltration. H&E: Haematoxylin &Eosin; PT: portal triad;
HP: hepatocytes; CV: central vein; IL: inammation.
Y. Kavitha, A. Geetha / Journal of Traditional and Complementary Medicine 8 (2018) 497e505 503
SOD, catalase, TBARS and 4-HNE. Depletion of antioxidant
enzymes GP
SOD, and catalase was seen in the pancreatic tissue
and blood of the EtOH and cerulein administered rats. The levels
were restored in MEMARB co-administered rats. A signicant drop
in the molecular antioxidant GSH and an elevation in the lipid
peroxidation products malondialdehye and 4-HNE were noted in
the results obtained from the pancreatitis-induced group. With
MEMARB treatment the level of GSH increased and the levels of
malondialdehye and 4-HNE decreased to relatively normal levels.
MEMARB with a large number of polyphenols like quercetin could
be responsible for this antioxidant effect.
Oxyresveratrol from
Morus alba root cortex is a potent lipid peroxidation inhibitor evi-
denced by the inhibitory effect against FeSO4/H2O2-induced
microsomal peroxidation. It has also been shown to scavenge
DPPH radical in vitro.
A present review indicates that the root
barks of Morus plants contain diverse polyphenols such as Diels-
Alder-type adducts, derivatives of benzofuran, stilbenes and poly-
hydroxylated alkaloids in addition to avonoids.
Generally poly-
phenols are hydroxyl group containing polar compounds which can
donate the protons to neutralize the toxic free radicals. Hence, the
antioxidant potential of the test compound could be attributed to
the presence of polyphenols.
Histopathological observations of pancreas and liver sections
from the respective experimental groups reinforce ndings from
the biochemical investigations. When compared to the normal
control and the drug control groups, the liver and pancreas sections
from the diseased group show inammatory inltrates and the
pancreas shows brotic changes. Sections of liver and pancreas
from the MEMARB treated group show restored tissue architecture
with a signicant reduction in leukocyte inltration and only mild
brosis in the pancreas proving the pancreato-protective effect of
5. Conclusion
This is the pilot study which authenticates the anti-
inammatory activity of phytonutrients present in the root bark
extract of Morus alba. The anti-inammatory property observed in
this study might be due to the effect of avonoids which could
intervene in the formation of cytokines. This study represents the
preventive effect of Morus alba on the development of pancreatitis.
However, as a future perspective, the same study can be applied on
animals with fully developed pancreatitis which would prove its
curative effect.
Conicts of interest
The authors declare no competing interests.
Funding source
This research did not receive any specic grant from funding
agencies in the public, commercial or not-for-prot sectors.
We are grateful for the generous gift of Cudraavone B from Dr.
Karel Smejkal, Associate Professor, Department of Natural Drugs,
Faculty of Pharmacy, University of Veterinary and Pharmaceutical
Sciences, Brno, Czech Republic.
The authors thank the Sophisticated Analytical Instruments
Facility, Indian Institute of Technology-Madras, Chennai, India, for
providing the infrastructure and technical support for the GC-MS
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... Phenolic acids in mulberry are attributed to hydroxycinnamic acid and benzoic acid derivatives (Yuan & Zhao, 2017). The mulberry plant and various functionalities pertain with essential functions of fruit, leaves, and the root bark establishing versatility (Kavitha & Geetha, 2018;Zhang, Ren, et al., 2014). Maintaining the perseverance of mulberry fruits with concomitant functional reservations renders the post-harvest elongations optimally (Wang, Sun, et al., 2015). ...
... For several decade, owing to the better safety profile, medicinal plant-derived natural products have excellent sources of therapeutic drugs for various diseases including cancer. 18,19 Root bark of mulberry (Morus alba L.) has been employed as natural product medicine with various therapeutic activities such as antioxidation, 20 anti-inflammation, 21 neuroprotection, 22 immunomodulation, 23 and antiatherosclerosis, 24,25 antiobesity, 25 antitumor, 26 antidepressant, 27,28 antihyperglycemic, and hypolipidemic activities. 29 Among various constituents of Morus alba, including Kuwanon derivatives such as Kuwanon-C, and G have shown anticancer activity. ...
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Medicinal plants from the family Moraceae have diverse applications in agriculture, cosmetics, food, and the pharmaceutical industry. Their extensive spectrum of pharmacological activity for treating numerous inflammatory illnesses, cancer, cardiovascular diseases, and gastrointestinal problems reflects their biological and therapeutic value. This article summarizes the molecular mechanisms related to the biological implications of mulberry extracts, fractions, and isolated bioactive compounds from different parts in various health‐related ailments. Additionally, the food industry and animal nutrition applications are summarized. Phytochemicals such as steroids, saponins, alkaloids, glycosides, polysaccharides, and phenolic compounds including terpenoids, flavonoids, anthocyanins, and tannins are found in this medicinal plant. The aqueous, ethanolic, and methanolic extracts, as well as bioactive compounds, have anti‐oxidative, hypoglycemic, nephroprotective, antimicrobial, neuroprotective, anti‐mutagenic, hepatoprotective, anthelmintic, immune‐modulatory, cardioprotective, and skin protecting activities. Mulberry supplementation in food products improves the stability of phenolics, sensory properties, antioxidant activity, and antimicrobial properties. Mulberry leaves in animal feed increase the nutrient digestibility, growth parameters, antimicrobial, and antioxidant properties. Practical applications This review summarized the in vivo and in vitro biological activities of the mulberry and isolated constituents in various health conditions. In addition, the food uses such as antioxidant potential, antimicrobial, and physicochemical properties were discussed. Furthermore, in vivo studies revealed mulberry as a significant protein source and its flavonoids as potential animal foliage.
The inflammasome is a cytosolic multiproteic complex that promotes proinflammatory events through the release of the cytokines IL-1β and IL-18, and in some context by the induction of a lytic cell death called pyroptosis, in response to damage, infections, or changes in the homeostasis. Due to the powerful inflammatory effect, there are several regulatory mechanisms that are essential to modulate or limit the activation of the inflammasome. When these mechanisms fail, the deregulation of the complex leads or contributes to the development of a plethora of diseases characterized by constitutive and/or chronic inflammation, such as autoinflammatory, autoimmune, cardiovascular, neurodegenerative, and metabolic diseases, cancer, or even severe complications of infectious diseases. Either environmental or genetic factors may affect the threshold and/or the level of inflammasome activation, such as hyperglycemia, hyperuricemia, auto-antibodies, unfolded proteins and fibrils, or individual genetic variants in genes coding for inflammasome receptors or effector molecules, and also in regulators. While the genetics of inflammasome itself has been elsewhere characterized and also recently reviewed by our group, less is known about how genetic variants in regulatory molecules could affect inflammatory diseases. Therefore in this work, we selected a group of known or possible regulators of the inflammasome, and through the review of genetic association studies we tried to depict the contribution of these regulators in the development of multifactorial diseases.
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Background and Objective: Pesticides exposure has been reported as an environmental factor that increases the risk of developing serious health problems. Glyphosate is one of the most widely used pesticides in the world. In the present work, in vivo biochemical and histological study of the hepatotoxic effect of glyphosate on liver rats has been first demonstrated. In addition, Morus alba leaves extract have been evaluated for their protective effect against this herbicide toxicity. Materials and Methods: Daily dose of 100 mg kgG1 b.wt., of glyphosate was administered to rats by intraperitoneal injection. Then, liver functions were evaluated biochemically and histopathologically by measuring biomarkers of oxidative stress and by visualizing the effect of herbicide administration on histological sections. Results: Treatment of adult rats with Glyphosate solution resulted in increased serum AST and ALT levels and lipid peroxidation (MDA), altered SOD, POD and CAT activities significantly compared to the normal (control group) and increased CRP levels, a reference indicator of inflammation. Similarly, histological sections revealed vacuolar degeneration of liver cells with focal necrosis in Glyphosate treated rats. MALE treatment preserved the biochemical and histological damage caused by Glyphosate toxicity at near�normal levels. Conclusion: The present work concludes that MALE due to its rich phenolic composition could exert a hepatoprotective role as an antioxidant and anti-inflammatory against Glyphosate-induced oxidative stress.
Background: Enhancing blood flow and cell proliferation in the hair dermis is critical for treating hair loss. This study was designed to aid the development of alternative and effective solutions to overcome alopecia. Specifically, we examined the effects of Morus alba. L root extract (MARE, which has been used in traditional medicine as a stimulant for hair proliferation) on dermal fibroblasts and other cell types found in the epidermis. Methods: We first optimized the concentration of MARE that could be used to treat human dermal fibroblasts (HDFs) without causing cytotoxicity. After optimization, we focused on the effect of MARE on HDFs since these cells secrete paracrine factors related to cell proliferation and angiogenesis that affect hair growth. Conditioned medium (CM) derived from MARE-treated HDFs (MARE HDF-CM) was used to treat human umbilical vein endothelial cells (HUVECs) and hair follicle dermal papilla cells (HFDPCs). Results: Concentrations of MARE up to 20 wt% increased the expression of proliferative and anti-apoptotic genes in HDFs. MARE HDF-CM significantly improved the tubular structure formation and migration capacity of HUVECs. Additionally, MARE HDF-CM treatment upregulated the expression of hair growth-related genes in HFDPCs. CM collected from MARE-treated HDFs promoted the proliferation of HFDPCs and the secretion of angiogenic paracrine factors from these cells. Conclusion: Since it can stimulate the secretion of pro-proliferative and pro-angiogenic paracrine factors from HDFs, MARE has therapeutic potential as a hair loss preventative.
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Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-L-arabinopyranoside (1), (9R)-moracin P 9-O-β-D-glucopyranoside (2), (9R)-moracin P 3′-O-β-D-glucopyranoside (3), and (9R)-moracin O 10-O-β-D-glucopyranoside (4) based on the spectroscopic interpretation and chemical analysis. Three benzofuran-type stilbenes, moracin O (5), R (7), and P (8) showed significant neuroprotective activity against glutamate-induced cell death in SK-N-SH cells. In addition, moracin O (5) and P (8) also demonstrated a remarkable inhibition of the acetic acid-induced pain. The molecular docking with metabotropic glutamate receptor 1 (mGluR1) results indicated that these neuroprotective benzofuran-type stilbenes might be the active analgesic components of the genus Morus, and acted by mediating the mGluR1 pathway.
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Aberrant activation of inflammation and excess accumulation of lipids play crucial role in the occurrence and progression of atherosclerosis (AS). Quercetin (QCT) has been tested effectively to cure AS. It is widely distributed in plant foods and has been proved to have potential antioxidative and anticancer activities. However, the underlying molecular mechanisms of OCT in AS are not completely understood. In the present study, we stimulated murine RAW264.7 cells with lipopolysaccharide (LPS) or oxidized low-density lipoproteins (ox-LDL) to mimic the development of AS. The data show that QCT treatment leads to an obvious decrease of multiple inflammatory cytokines in transcript level, including interleukin (IL)-1α, IL-1β, IL-2, IL-10, macrophage chemoattractant protein-1 (MCP-1), and cyclooxygenase-2 (COX-2) induced by LPS. Moreover, expressions of other factors that contribute to the AS development, such as matrix metalloproteinase-1 (MMP-1) and suppressor of cytokine signaling 3 (SOCS3) induced by LPS are also downregulated by QCT. Furthermore, we found that QCT suppressed LPS-induced the phosphorylation of STAT3. Meanwhile, QCT could ameliorate lipid deposition and overproduction of reactive oxygen species induced by ox-LDL, and block the expression of lectin-like oxidized LDL receptor-1 (LOX-1) in cultured macrophages. Taken together, our data reveal that QCT has obvious anti-inflammatory and antioxidant virtues and could be a therapeutic agent for the prevention and treatment of AS.
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Morus, a plant genus from the family of Moraceae, most plants of which are used as traditional medicines in Asian counties. The root barks of Morus plants are normally called as Sang-Bai-Pi (SBP) in Chinese and used for the treatment of inflammatory and respiratory diseases. Decades of research on phytochemistry of SBP have led to the identification of various compounds, such as Diels–Alder-type adducts, flavonoids, benzofurans, stilbenes, polyhydroxylated alkaloids, etc. These compounds have showed a wide range of bioactive features including anti-inflammatory, anti-oxidative, anti-microbic, etc. This review focus on the bioactive compounds and their pharmacological effects of SBP which will help us fully understand the effective substances of SBP, and pave our way to further explore medicinal uses of SBP and comprehensive utilization of Morus species.
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The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties.
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In this review we summarize the role of inflammasomes in pancreatic physiology and disease with a focus on acute pancreatitis where much recent progress has been made. New findings have identified inducers of and cell specificity of inflammasome component expression in the pancreas, the contribution of inflammasome regulated effectors to pancreatitis, and metabolic regulation of inflammasome activation which are strong determinants of injury in pancreatitis. New areas of pancreatic biology will be highlighted in the context of our evolving understanding of gut microbiome and injury induced inflammasome priming, pyroptosis, and innate immune mediated regulation of cell metabolism. Copyright © 2015, American Journal of Physiology- Gastrointestinal and Liver Physiology.
Heat stroke is characterilized by hyperthermia, systemic inflammation, and multiple organ failure including arterial hypotension. This definition can be fulfilled by a rat model of heat stroke used in the present study. Anesthetized animals were exposed to heat exposure (43 °C for 70 min) and then returned to room temperature (26 °C) for recovery. One hour before heat exposure, an intraperitoneal dose of quercetin (30 mg/kg) or vehicle (normal saline 1 ml/kg) was administered to the experimental groups of rats. Additional injection was administered immediately after the onset of heat stroke. Immediately after the onset of heat stroke. Vehicle-treated rats displayed (i) hyperthermia; (ii) suppressed left ventricular function; (iii) decreased contents of cardiac total antioxiant capacity (e.g., superoxide dismutase, glutathione peroxidase, catalase); (iv) increased contents of cardiac oxidative capacity malondialdehyde and thiobarbituric acid reactive substances; (v) increased cardiac levels of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6; and (vi) decreased cardiac levels of an anti-inflammatory cytokine interleukin 10. Histopathologic and survival observation provided supportive evidence for biochemical analyses. These heat stroke reactions all can be significantly attenuated by quercetin therapy. Our data suggest that quercetin therapy might improve outcomes of heat stroke in rats by attenuating excessive hyperthermia as well as myocardial injury. The protective effects of quercetin could be attributed to anti-lipid peroxidative, anti-oxidant, and anti-inflammatory properties.
Volume III of this manual provides an overview of the analytical investigation of 23 additional Chinese Herbal Drugs, which are most commonly used in Traditional Chinese Medicine. Together with Volumes I and II this current volume represents the most comprehensive overview to analytical studies of those herbal drugs. The quality proof of the investigation meets the standard of the European Drug Regulatory Authority. The authors refer to the bioactive constituents, pharmacological and biological activities of all single herbal drugs, as well as their therapeutic applications. Analytical methods applied are described in detail.