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\begin{document}


\def\RunningAuthor{Poojitha M et al.}
\firstPage{2519}
\articleType{Original Article}
\receivedDate{27 Feb 2020}
\acceptedDate{14 Apr 2020}
\revisedDate{21 Mar 2020}
\journalVolume{2020, 11}
\journalIssue{2}
\journalDoi{ijrps.v11i2.2247}
\copyrightYear{2020}
\def\authorCount{3}
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\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{Gastroprotective effect of leaves of \textit{Breyniavitis-Idaea }}
\author{Poojitha~M\textsuperscript{*}\textsuperscript{1},  
            Saravanakumar~A\textsuperscript{2}, 
            Satyanarayana~S~V\textsuperscript{3}~\\[5pt]{\textsuperscript{1}Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University Anantapur, Ananthapuramu, Andhra Pradesh, India}~\\{\textsuperscript{2}Department of Pharmacology, Sri Venkateswara College of Pharmacy, RVS Nagar, Chittoor, Andhra Pradesh, India}~\\{\textsuperscript{3}Department of Chemical Engineering, Jawaharlal Nehru Technological University Anantapur, Ananthapuramu, Andhra Pradesh, India}}

\begin{abstract}
Due to the lure backs of synthetic drugs that are being used medical field has turned over to the traditional medicine which are devoid of side effects and major adverse effects. So that Herbal drugs were seen as probable replacements for the handling of PUD without showing side effects and equaling the treatment efficacy. The literature review on investigations of antiulcer activity of various plant drug, the present investigation was carried out to investigate the antiulcer potential, chemical constituents present in the methanol extract of traditional plant Breyniavitis-idaea. Gastric ulcers in experimental animals were brought by four different models like  Ethanol(Alcohol)   induced, NSIDS (Indomethacin) induced, Pylorus ligation method and Cold resistant stress induced method by comparing with the standard drug namely omeprazole (20mg/kg) which exhibited the dose dependent capacity of the extract (125mg/kg,250mg/kg, 500mg/kg) and also the biochemical parameters like ALP, GSH, pH and Gastric volume contents were estimated in all the selected groups (Design of Experiment). The results obtained from the study has helped to identify that 500mg/kg of plant extract has gastro protective effect in all the chosen models in comparison to the omeprazole (20mg/kg) standard drug. Owing to the prevalence of different phytoconstituents like poly phenols and flavonoids shown the dose dependent potent gastroprotective activity.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Breyniavitis-idaea,\newline Ethanol induced,\newline Indomethacin induced,\newline Pylorus ligation,\newline Cold resistant stress,\newline Dose Dependent
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Poojitha~M~\\ Phone:\ 8332063418~\\  Email:\ poojithamallapu91@gmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{Introduction}
PUD (Peptic Ulcer Disease) distresses most of the people in the world and disabling their daily activities. It is noted as one the commonest and stubborn diseases that occur in people and affect their lives \unskip~\citep{742664:17641125}. 

There are various factors involved to cause the disease such as oxidative stress, chronic and excessive smoking, malnutrition and due to chronic use drugs like NSAID's and steroids. The imbalances in the offensive and defensive factors like HCl, enzymes, H. Pylori and Mucin, prostaglandins NO2 and carbonates and bicarbonates act as common factors in causing the PUD \unskip~\citep{742664:17641121,742664:17641133,742664:17641129,742664:17641119}.

One of the major setbacks of the PUD treatment is the incidence and development of drug tolerance and others being relapse of disease, noting of side effects on clinical observation after treatment. 


\begin{table*}[!htbp]
\caption{\boldmath {Gastroprotective Effect of \textit{MEBV} in experimental animals} }
\label{tw-51da4be1e32e}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.15900000000000002\linewidth-2\tabcolsep}p{\dimexpr.08099999999999998\linewidth-2\tabcolsep}p{\dimexpr.12\linewidth-2\tabcolsep}p{\dimexpr.12\linewidth-2\tabcolsep}p{\dimexpr.12\linewidth-2\tabcolsep}p{\dimexpr.12\linewidth-2\tabcolsep}p{\dimexpr.12\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\multicolumn{8}{p{\dimexpr(1\linewidth-2\tabcolsep)}}{\cAlignHack Gastroprotective Effect of MEBV in experimental animals}\\
\tblmidrule 
\multicolumn{1}{p{\dimexpr(.15900000000000002\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{Cold-Restraint}} &
    (\% I) &
  NA &
  No inhibition &
  49.51 &
  59.00 &
  73.73 &
  79.32\\
 &
  UI &
  No ulcerous lesions &
  11.27 + 1.52 &
  5.69+ 0.33* &
  4.62+ 0.37* &
  2.96 + 0.41** &
  2.33 + 0.39**\\
\multicolumn{1}{p{\dimexpr(.15900000000000002\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{Pylorus ligation}} &
    (\% I) &
  NA &
  No inhibition &
  33.85 &
  58.96 &
  73.60 &
  77.74\\
 &
  UI &
  No ulcerous lesions &
  18.64 + 0.52 &
  12.33 + 0.41* &
  7.65 + 0.47** &
  4.92 + 0.19** &
  4.15 + 0.28**\\
\multicolumn{1}{p{\dimexpr(.15900000000000002\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{Indomethacin}} &
    (\% I) &
  NA &
  No inhibition &
  48.732 &
  59.923 &
  70.481 &
  75.900\\
 &
  UI &
  No ulcerous lesions &
  7.76 \ensuremath{\pm} 0.720 &
  4.90 \ensuremath{\pm} 0.352* &
  4.01 \ensuremath{\pm} 0.35** &
  3.04 \ensuremath{\pm}0.58** &
  2.48 \ensuremath{\pm} 0.421**\\
\multicolumn{1}{p{\dimexpr(.15900000000000002\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{Ethanol model}} &
    (\% I) &
  NA &
  No inhibition &
  42.420 &
  58.32 &
  70.044 &
  75.280\\
 &
  UI &
  No ulcerous lesions &
  18.69 \ensuremath{\pm} 1.420 &
  10.35 \ensuremath{\pm} 0.391* &
  8.04 \ensuremath{\pm} 0.460** &
  4.57 \ensuremath{\pm}0.844** &
  4.62 \ensuremath{\pm}0.491**\\
\multicolumn{2}{p{\dimexpr(.24\linewidth-2\tabcolsep)}}{Group} &
  I~&
  II &
  III &
  IV &
  V &
  VI\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{(\% I= Percentage of inhibition, UI= Ulcer index)}
    
\item{Data be situated epitomized as mean \ensuremath{\pm} S.E.M, ANOVA shadowed by Dunnett's multiple comparison test. \ensuremath{^{*}}P \textless\ 0.01 and \ensuremath{^{**}}P\textless\ 0.001 as equated to control (n = 6 in each group)}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Effect of MEBV on GSH (\ensuremath{\mu}g/mg protein)} }
\label{tw-0e3fae941740}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.09739999999999998\linewidth-2\tabcolsep}p{\dimexpr.2296\linewidth-2\tabcolsep}p{\dimexpr.2482\linewidth-2\tabcolsep}p{\dimexpr.20990000000000002\linewidth-2\tabcolsep}p{\dimexpr.2149\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Group & Alcohol persuaded gastric ulcer model & NSAIDS persuaded gastric ulcer model & Pylorus ligation Persuaded ulcer model & Cold-restraint stress persuaded Gastric ulcer  model\\
\tblmidrule 
I &
  2.87\ensuremath{\pm} 0.330 &
  3.05\ensuremath{\pm} 0.221 &
  2.75\ensuremath{\pm} 0.222 &
  2.94\ensuremath{\pm} 0.285\\
II &
  0.97\ensuremath{\pm} 0.270 &
  0.92\ensuremath{\pm} 0.272 &
  0.81\ensuremath{\pm} 0.26 &
  0.94\ensuremath{\pm} 0.352\\
III &
  1.31\ensuremath{\pm} 0.321* &
  1.35\ensuremath{\pm} 0.171* &
  1.35\ensuremath{\pm} 0.22* &
  1.54\ensuremath{\pm} 0.172*\\
IV &
  1.37\ensuremath{\pm} 0.220** &
  1.54\ensuremath{\pm} 0.122** &
  1.52\ensuremath{\pm} 0.37** &
  1.65\ensuremath{\pm} 0.371**\\
V &
  1.65\ensuremath{\pm} 0.890** &
  1.69\ensuremath{\pm} 0.220** &
  1.74\ensuremath{\pm} 0.33** &
  1.82\ensuremath{\pm} 0.330**\\
VI &
  1.77\ensuremath{\pm} 0.331** &
  1.76\ensuremath{\pm} 0.240** &
  1.78\ensuremath{\pm} 0.24** &
  1.87\ensuremath{\pm} 0.220**\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{All the numbers set were expressed as mean \ensuremath{\pm} SEM.*P\textless\ 0.01 when compared with control group.P\textless\ 0.01 when compared with normal group}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Effect of MEBV on ALP (IU/L) of gastric ulcer persuaded models} }
\label{tw-410cc233488f}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.09519999999999998\linewidth-2\tabcolsep}p{\dimexpr.25450000000000003\linewidth-2\tabcolsep}p{\dimexpr.24029999999999998\linewidth-2\tabcolsep}p{\dimexpr.205\linewidth-2\tabcolsep}p{\dimexpr.205\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Group  & Alcohol persuaded gastric ulcer model & Indomethacin persuaded gastric ulcer model & Pylorus ligation persuaded ulcer model & Cold-restraint stress persuaded Gastric ulcer model\\
\tblmidrule 
I &
  68.22\ensuremath{\pm} 2.54 &
  59.24\ensuremath{\pm} 2.21 &
  70.29\ensuremath{\pm} 2.32 &
  76.47\ensuremath{\pm} 2.46\\
II &
  179.54\ensuremath{\pm} 2.33 &
  188.19\ensuremath{\pm} 3.42 &
  195.67\ensuremath{\pm} 3.38 &
  204.22\ensuremath{\pm} 3.52\\
III &
  123.64\ensuremath{\pm} 2.43* &
  120.14\ensuremath{\pm} 3.52* &
  130.41\ensuremath{\pm} 3.22* &
  130.19\ensuremath{\pm} 2.76*\\
IV &
  113.35\ensuremath{\pm} 2.58** &
  115.22\ensuremath{\pm} 2.32** &
  116.52\ensuremath{\pm} 2.41** &
  120.49\ensuremath{\pm} 2.33**\\
V &
  82.45\ensuremath{\pm} 1.48** &
  86.33\ensuremath{\pm} 1.24** &
  85.22\ensuremath{\pm} 1.57** &
  98.27\ensuremath{\pm} 1.67**\\
VI &
  79.54\ensuremath{\pm} 1.12** &
  83.21\ensuremath{\pm} 1.54** &
  82.12\ensuremath{\pm} 1.33** &
  89.37\ensuremath{\pm} 1.19**\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{All values in the statistics set were expressed as mean \ensuremath{\pm} S.E.M.*P\textless\ 0.01 when equated with control group. P\textless\ 0.01 when compared with normal set}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Effect of MEBV on Gastric volume (ml/100g) } }
\label{tw-8f046cb024f6}
\centering 
\begin{threeparttable}

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\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.10089999999999998\linewidth-2\tabcolsep}p{\dimexpr.24820000000000004\linewidth-2\tabcolsep}p{\dimexpr.2044\linewidth-2\tabcolsep}p{\dimexpr.22660000000000004\linewidth-2\tabcolsep}p{\dimexpr.2199\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Group  & Alcohol made gastric ulcer model & NSAIDS made gastric ulcer model & Pylorus ligation made ulcer model & Cold-restraint stress  made Gastric ulcer model\\
\tblmidrule 
I &
  0.38 \ensuremath{\pm}0.03 &
  0.36 \ensuremath{\pm}0.02 &
  0.45 \ensuremath{\pm}0.02 &
  0.57 \ensuremath{\pm}0.02\\
II &
  2.66 \ensuremath{\pm}0.05 &
  2.39 \ensuremath{\pm}0.01 &
  2.47 \ensuremath{\pm}0.03 &
  2.57 \ensuremath{\pm}0.05\\
III &
  1.12 \ensuremath{\pm}0.84* &
  1.02 \ensuremath{\pm}0.03* &
  1.17 \ensuremath{\pm}0.02* &
  1.22 \ensuremath{\pm}0.03*\\
IV &
  0.93 \ensuremath{\pm} 0.87** &
  0.91 \ensuremath{\pm}0.05** &
  0.99\ensuremath{\pm}0.05** &
  0.92\ensuremath{\pm}0.05**\\
V &
  0.68 \ensuremath{\pm} 0.91** &
  0.64 \ensuremath{\pm}0.05** &
  0.69 \ensuremath{\pm}0.03** &
  0.69\ensuremath{\pm}0.02**\\
VI &
  0.54 \ensuremath{\pm}0.05** &
  0.54\ensuremath{\pm}0.03** &
  0.57 \ensuremath{\pm}0.05** &
  0.58 \ensuremath{\pm}0.05**\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{All values in the data set were articulated as mean \ensuremath{\pm} S.E.M.*P\textless\ 0.01 when equated with control group. P\textless\ 0.01 when equated with normal group}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Effect of MEBV on pH of gastric contents} }
\label{tw-7031aab194eb}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.10169999999999998\linewidth-2\tabcolsep}p{\dimexpr.21119999999999997\linewidth-2\tabcolsep}p{\dimexpr.23240000000000002\linewidth-2\tabcolsep}p{\dimexpr.2265\linewidth-2\tabcolsep}p{\dimexpr.2282\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Group  & Alcohol persuaded gastric ulcer model  & Indomethacin persuaded gastric ulcer model & Pylorus ligation persuaded ulcer model & Cold-restraint stress persuaded Gastric ulcer model \\
\tblmidrule 
I &
  5.11 \ensuremath{\pm}0.19 &
  5.60 \ensuremath{\pm}0.33 &
  5.61 \ensuremath{\pm}0.41 &
  5.67 \ensuremath{\pm}0.22\\
II &
  1.49 \ensuremath{\pm}0.33 &
  1.52 \ensuremath{\pm}0.21 &
  1.62 \ensuremath{\pm}0.22 &
  1.58 \ensuremath{\pm}0.12\\
III &
  3.74\ensuremath{\pm}0.12* &
  3.90 \ensuremath{\pm}0.17* &
  3.58 \ensuremath{\pm}0.33* &
  3.69 \ensuremath{\pm}0.17*\\
IV &
  4.46 \ensuremath{\pm} 0.59** &
  4.50 \ensuremath{\pm}0.14** &
  4.48 \ensuremath{\pm}0.37** &
  4.45 \ensuremath{\pm}0.52**\\
V &
  4.84 \ensuremath{\pm} 0.31** &
  4.87 \ensuremath{\pm}0.22** &
  4.95 \ensuremath{\pm}0.19** &
  4.79 \ensuremath{\pm}0.37**\\
VI &
  5.22 \ensuremath{\pm}0.29** &
  5.17 \ensuremath{\pm}0.41** &
  5.22 \ensuremath{\pm}0.33** &
  5.33 \ensuremath{\pm}0.22**\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{All values in the data set were voiced as mean \ensuremath{\pm} S.E.M.*P\textless\ 0.01 when equated with control group. P\textless\ 0.01 when equated with normal group}
\end{tablenotes}
\end{threeparttable}

\end{table*}
These draw backs of synthetic drugs make the efficacy of drugs quite arguable. This triggered the scope for search and development of newer drugs that treat PUD. Herbal drugs were seen as potential alternatives for the treatment of PUD without showing side effects and equaling the treatment efficacy \unskip~\citep{742664:17641122,742664:17641124}. 

Following the literature review on investigations of antiulcer activity of various plant drug, the current study was used to explore the antiulcer potential, chemical elements present in the methanol extract of  leaves of Breynia vitis-idaea., (Family: Poaceae) and the same is being reported here \unskip~\citep{742664:17641127}.
    
\section{Materials and Methods}
\textbf{Collection and Authentication of the plant material}

The plant part of Breyniavitis-idaea (Family: Phyllanthaceae) leaves were obtained from Chittoor District, validated by Dr. Madhava Chetty, Asst Professor, Department of Botany, Sri Venkateswara university, Tirupati 517502, Andhra Pradesh, India.

\textbf{Animals Used}

Albino rats of either sex weighing 150{\textendash}200g were kept in a 12 h light or dark cycle at a constant moderate thermal condition at 25\ensuremath{^{\ensuremath{\circ }}}C with free access to libitum. 

\textbf{Acute toxicity study}

Acute toxic dose of methanol extract of leaves of Breynia vitis-idaea., (Family: Poaceae) were determined following OECD guideline no. 423 (Acute Toxic Class Method). Found that the test extracts weren't deadly or toxic to the experimental animals was smooth at 2000mg/kg dose. 

Ethical clearance was approved by IAEC (Institutional Animal Ethical Clearance) Reg No: SVCOP/IAEC/007/2016-17. 

\textbf{Design of Treatment}

Group I- control (1\%W/V CMC, 10 ml/kg b.w) p.o

Group II- Negative control (1\%W/V CMC, 10 ml/kg b.w) p.o

Group III- MEBV (125mg/kg b.w) p.o

Group IV- MEBV (250mg/kg b.w) p.o

Group V- MEBV (500mg/kg b.w) p.o

Group VI- Std.Omeprazole (20mg/kg b.w) p.o

\textbf{Ulcer inducing models}

\textbf{Ethanol Induced Gastric Ulcer}

8ml/kg of alcohol was administered to all the assemblies of rats excluding the assembly 1 for which is well thought-out as normal healthy group \unskip~\citep{742664:17641132,742664:17641138}. The ulcer catalog for to each rat was taken as the mean ulcer score \unskip~\citep{742664:17641136}.

\textbf{NSAIDS (Indomethacin) Induced Gastric Ulcer}

Ulcers lesions in the stomachs of experimental animals were induced with the help of indomethacin (40 mg/kg p.o) administered to all groups after fasting for 24h \unskip~\citep{742664:17641137}.

\textbf{Pyloric Ligation Induced Gastric Ulcer}

This procedure was not performed on normal healthy group (group 1). After 4h from surgery, animals were forfeited through cervical dislodgment and score of ulcers was noted on the dissevered stomachs \unskip~\citep{742664:17641139}.

\textbf{Cold-Restraint Stress-Induced Ulcers}

Followed as per \unskip~\citep{742664:17641141}.

\textbf{Measurement of ulcer index}

Ulcer index (UI), and percentage of inhibition of ulcer lesions (\%I) were calculated as described in \unskip~\citep{742664:17641135}.
\begin{eqnarray*}\%I=\frac{(USc-USt)}{USc}\times100 \end{eqnarray*}
\textbf{Statistical analysis }

All the numbers were articulated as mean \ensuremath{\pm} standard error mean (SEM). Implication of variances among the group was calculated by using ANOVA. 
    
\section{Results and \textbf{Discussion}}
The methanol extracts of leaves of Breynia vitis-idaea showed a certainly defensive effects contrary to ulcers persuaded by alcohol, NSAIDS (indomethacin), Pylorus ligation and cold restraint models. The release of free radicles is the mechanism seen in ethanol induced ulcers which can be further supported by its improved activity in pylorus ligated method \unskip~\citep{742664:17641123}. 

The extract valor has also had an asset to rise prostaglandins thereby constructing a mucosal layer for shielding the ulcer from any direct exposure to the acid which is apparent from indomethacin induced gastric ulceration model \unskip~\citep{742664:17641130}. 

The NSAID drug is a COX inhibitor which disrupts the membrane integrity and causing rupture in the flow of blood. The extract might have helped in production of endogenous prostaglandins for protecting the ulcers \unskip~\citep{742664:17641140,742664:17641126,742664:17641131}. Gastric ulceration made by cold restraint stress is undoubtedly facilitated by the upsurge in gastric motility, degranulation of mast cells, decreased gastric mucosal blood, lowering in the prostaglandin synthesis and excretion of glycoproteins in the mucus \unskip~\citep{742664:17641117,742664:17641134,742664:17641120,742664:17641128}. 

Any of the above factors could have played an important role in the formation of ulcers. Finally, the extract was proven to have antioxidant activity and it is proven successful in thwarting the ulcers produced due to the physical strain or stress which produces reactive oxygen species detrimental to the stomach lining \unskip~\citep{742664:17641118}.
    
\section{Conclusions}
MEBV has exhibited dose reliant inhibition in ethanol induced stomach ulcer lesions and stimulate the secretion of prostaglandins or possess prostaglandins like-substances reveals that the as a potent inhibitor of stomach mucosal abrasions caused by ethanol, indomethacin, pylorus ligation and cold-restraint stress in rats.  Further, our results support the ethnopharmacological claims of Breynia vitis-idaea  as potent anti-ulcer agent. Etiologies of ulcers produced in different ulcer models are different. The study concluded that MEBV and its dynamic constituents may emerge as more effective healing agent to counter gastric ulcer.

\textbf{Conflict of interest}

Authors affirm that No interest of conflicts. 
    

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