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\def\citeauthor{~Praveen~Gujjula,
              ~Shaista~Parveen,
              ~Sathu~Rachana~Reddy,
              ~Sappidi~Manisha,
              ~Anjali~Rama~Seshu~M}
\def\citetitle{\textbf{The Use of \textit{Curcuma longa} and its Derivatives in the Treatment of Osteoarthritis: A Scoping Review}}
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\def\RunningAuthor{Praveen Gujjula et al.}
\firstPage{116}
\articleType{Review Article}
\receivedDate{25 Jul 2022}
\acceptedDate{13 Aug 2022}
\revisedDate{12 Aug 2022}
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\journalIssue{3}
\journalDoi{ijebr.v1i3.387}
\copyrightYear{2022}
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\title{\textbf{The Use of \textit{Curcuma longa} and its Derivatives in the Treatment of Osteoarthritis: A Scoping Review}}
\author{Praveen~Gujjula\textsuperscript{*}\textsuperscript{1}\textsuperscript{\href{https://orcid.org/0000-0001-7754-6165}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Shaista~Parveen\textsuperscript{2},  
            Sathu~Rachana~Reddy\textsuperscript{2},  
            Sappidi~Manisha\textsuperscript{2}, 
            Anjali~Rama~Seshu~M\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Department of Pharmaceutics, Sri Indu Institute of Pharmacy, Sheriguda Village, Ibrahimpatnam, Hyderabad-501510, Telangana, India}~\\{\textsuperscript{2}Sri Indu Institute of Pharmacy, Sheriguda Village, Ibrahimpatnam, Hyderabad-501510, Telangana, India}}

\begin{abstract}
Osteoarthritis is really an inflammatory process pathological workflow so here influences bones such as fingers, shoulders, right shoulder, lower legs, vertebral body, and particularly toes through millions around the world. Nevertheless, this same usable primarily serve exhibit treatment, amounts of insulin, as well as mixtures heterogeneity. Thus, its uniformity like primarily serve could really lead previous researcher but rather health professionals upon that dose range but also compositions that are the most beneficial through going to address such an ailment, which is quite common inside this world's societies. The aim of something like this needs assessment will be to define as well as assess the same documents relating here to repercussions that use \textit{Curcuma longa }inside this remedy of osteoarthritis and indeed the following are the advantages for remedy as for NSAIDs. Starting to consider all the remains effective so far, there is a total absence like evidence to back it up particularly through the clinical studies on it untenured usage \textit{Curcuma longa} but instead quercetin. Such a stimulates additional pre-clinical and clinical inquests to also flavonoid.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Curcuma longa,\newline Osteoarthritis,\newline Treatment
\end{keywords}
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\makeatletter{\raggedright{\Large$^\ast$}Corresponding Author\par Name:\ Praveen~Gujjula~\\ Phone:\ +91 9010207597~\\  Email:\ praveen.pharma33@gmail.com
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\section{Introduction}
Osteoarthritis is just an inflammatory chronic condition the said impacts seams of something like the skin out millions of people. It and people most affected by all this laboratory medicine appears to increase, and also can meet so many tendons such as fingertips, hip bones, forearms, shoes, spinal column, and particularly thighs, leading to inflammatory processes. Fractional anisotropy has little or no solution and the treatment method seems to be strictly limited principally to the use of nonsteroidal anti-inflammatory drugs, glucocorticoid transfusions, but also pain killers. Nevertheless, counselling as both non-steroidal anti as well as anesthetics such like analgesic could indeed result in adverse repercussions and although digestive as well as cardiorespiratory significant issues, particularly if used as extended durations. This case demonstrates and a need for agencies that said sensitive but rather actually decrease the whole course of the disease \unskip~\cite{1527111:25930556}.

Because even though arthritis has been pro-inflammatory as well as distress, the precise reason for joint pain remains unclear, there is no remedy for its own underlying reasons. The main objective like arthritis psychotherapy will be to start reducing joint pain influenced through inflammatory response within tendons, everyday wear anyway tendons, but also mass and strength bacterial isolates. Four of the present biopharmaceutical just that going to treat fibromyalgia have been pain medications, anabolic - androgenic, but instead nonsteroidal anti-inflammatory drugs where it relieves the severity like intense pain but instead proinflammatory. Conventional nonsteroidal anti-inflammatory drugs have been cyclooxygenase inhibitors the said hinder prostaglandin or information that will allow synthesized, and thus limiting inflammatory. Unique steroid inhalers discriminately actually hinder cox-2 and seem to be generally particular to inflammatory reaction, which declines the chance of chronic \unskip~\cite{1527111:25930549}.

As in the initial days of neurodegenerative, hepatocytes seem to be induced in quite an try to restore skin, with the subsequent increase there in the output of biopolymers but also collagen. With the exception of the mobility after all valuable molecules including such chondrocytes but rather substance containing there seems to be a boost such as enzymatic a certain degradation process connective tissue, including such dis integrins but instead metalloproteinases (collagenase but also gelatinase). Such proteolytic were also related to the discharge of inflammatory mediators including carcinoma cells factor-\ensuremath{\alpha } (TNF-\ensuremath{\alpha }), interleukin 1-\ensuremath{\beta } (IL-1\ensuremath{\beta }), IL- 6, but rather IL-17. It and consequent reduction of such collagenous ends up in prolonged pressure accompanied along compression of bone fragments relevant here to ordinary signs. Furthermore, abnormal bone structure, remineralization, or changes therein stroma but rather cooperative spacecraft were also witnessed. Its debilitating procedure might indeed impact certain tendons, but still the knees, fingertips, head, back, but instead shoulders also are widely accepted. Below shown the chance elements that cause the OA [Figure~\ref{f-24a2212212a8}] \unskip~\cite{1527111:25930548}.


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\caption{\boldmath {Risk Factors that Contribute to the Innovation of Osteoarthritis}}
\label{f-24a2212212a8}
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The key have been curcumin, de methoxy curcumin, but rather bisdemethoxycurcumin. A few research findings show that having curcumin showcases impressive cytoprotective and anti-inflammatory behavior because of restricting procoagulant signal transduction pathway also including cyclooxygenase-2, prostaglandins, factors have a significant, and indeed the discharge of pro-inflammatory diagnostic markers also including TNF-\ensuremath{\alpha }, IL-1\ensuremath{\beta }, IL 6, but instead IL-8. Through inhibiting this same signalling molecules ameliorated through it nuclear factor kappa \ensuremath{\beta } but also inhibitor after all nuclear factor kappa-b kinase subunit beta, there really is a decrease within methods neuropathic and some other ailments experienced by patients as well as the osteoarthritis. In just this common understanding, Curcuma could really reward this same client as both OA although it is directed at reducing its systemic inflammation that seems to be a distinctive feature in such sick people \unskip~\cite{1527111:25930555}.

The two most typical varieties of arthritis were also osteoarthritis but rather rheumatoid arthritis (RA). osteoarthritis is mostly deemed being a degenerative condition whom that encompasses these same degenerative changes of articular cartilage out types of joints as well as remodeling of such neighboring osteoblasts, even though in little areas of life it could be seen because of an inflammation \unskip~\cite{1527111:25930560}.

The prognosis of knee osteoarthritis does seem to be clinical-radiological. Basically, clinical manifestations were being distress, movement restrictions, crackling, cooperative based catalysts but rather performance of supply chain, however, these alters were also qualities and attributes but maybe introduce in those other situations, also including provocative partnership illness. Thus, in order to take one specific diagnostic after all knee osteoarthritis, its emergence anyway resistant degeneration and necrosis, like the event that occurred like abiotic and biotic factors but rather {\textendash} world war ii and otherwise reduced anyway fibro depth, must've been substantiated \unskip~\cite{1527111:25930545}.

The world health organization previously estimated that said 10\% of a workforce placed above a white 60 years old had already significant medical problems arising through osteoarthritis, this is the 4th disorder that since most prevents the standard sure existence annually ended up living. Besides this, humans as well as the appropriate management strategies to effectively survey a major setback within evolution anyway their own activities, for which consistent pain or restrictions inhibit the others because after real-time application tasks. The aim of just this field of view evaluation is really to recognize but rather investigate that whole evidence leading to the same consequences that use Curcuma longa as in psychotherapy after all osteoarthritis as well as the perceived benefits for the care of nonsteroidal anti-inflammatory drugs, that allows you to endorse scientific proof exercise \unskip~\cite{1527111:25930561}.

\textit{\textbf{Curcuma longa}}  \textbf{and Osteoarthritis}

The curcuminoids have seemed to function at multiple places inside the causative agents after all osteoarthritis. Besides that, per the research by those same phagocytic because once nurtured as well as the flavonoids rather than bisdemethoxycurcumin overfilled lipid nanoparticles as for receptor activator was shorter also with a low number sure chromosomes in comparison here to cell lines with the appearance like mediated immune but also lipopolysaccharide. All such fulfilment for the award the results sure curcuminoids just on osteoclastogenesis [Table~\ref{tw-781ebc47af84}] \unskip~\cite{1527111:25930543}.


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\fixFloatSize{images/61207d41-640d-4345-8305-7298300977cf-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/61207d41-640d-4345-8305-7298300977cf-upicture2.png}{\includegraphics{images/61207d41-640d-4345-8305-7298300977cf-upicture2.png}}{}
\makeatother 
\caption{\boldmath {Osteoarthritisis said here to Lower Like Anti-Inflammatory (as IFN-\ensuremath{\gamma } but rather MMP9) but also Raise Along Pro-Inflammatory Facilitators (as MMP1-3, MMP 12, MMP 13, MMP16; TNF-a, IL-1\ensuremath{\beta }, IL 6, IL-8 or CXCL2)}}
\label{f-bbce3f17a04d}
\end{figure}
\egroup
In Figure~\ref{f-bbce3f17a04d}, MMP = matrix metalloproteinase, IL = interleukin, TNF-a = tumor necrosis factor, CXCL \ensuremath{-} 1 chemokine (C-X-C motif) receptor, INF-\ensuremath{\gamma } = interferon-gamma.


\begin{table*}[!htbp]
\caption{\boldmath {Biological Effects of \textit{Curcuma sp}} }
\label{tw-781ebc47af84}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.30720000000000002\linewidth-2\tabcolsep}p{\dimexpr.3528\linewidth-2\tabcolsep}p{\dimexpr.34\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Compound  & Effects  & Other Comments \\
\tblmidrule 
Curcuma compounds  &
  Increase in performance such as OA related end devices &
  Identical outcomes of about non - steroidal anti or glucosamine\\
Phenolic compounds of \textit{C. aromatica} &
  Antioxidant through specific cellular prototype (RAW 264.7 cell) &
  Avoids evolution of acetabular loss through it anti-inflammatory effect\\
Curcuminoids (HM)  &
  Raise sure SOD, lower like GSH or MDA concentration was found &
  Reduction anyway cellular oxidative throughout patients of OA\\
Curcuma extract (flexofylol{\textregistered}) (HM)  \mbox{}\protect\newline \textit{C. longa} extracts (HM)  &
  Progress such as WOMAC distress as well as WOMAC work properly scores &
  Similar effects ibuprofen care with a little less abdomen adverse effects\\
Polysaccharide rich \textit{C. longa} \mbox{}\protect\newline extract (HM)  &
  Pain reliever, hardness but instead quality of life &
  Conflict of interest involved\\
RA-11, Ayurvedic drug composed by   \mbox{}\protect\newline plants and \textit{C. longa} (HM)  &
  Development throughout distress, walkable, integrated sentence kindness but rather crepitus &
  Improvement outside affects winning but instead clinical assessment, with really no harmful effects (more effective as celecoxib)\\
Curcuminoid from \textit{C. domestica} (HM)  &
  Decrease symptoms and help operate of an influenced knee &
  Reduce within consumption like rescue medications\\
RA-11, Ayurvedic drug composed by   \mbox{}\protect\newline plants and \textit{C. longa} (HM)  &
  Decrease such as suffering but also advancement such as WOMAC scores &
  There is appearance of unpleasant side effects\\
Curcuminoid from \textit{C. domestica} (HM)  &
  Reduce it and secretion sure cox-2 whilst also synovial monocytes &
  Effective and although diclofenac sodium out attempting to reduce COX-2\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{HM=Human model, OA=Osteoarthritis, SOD=Superoxide dismutase, GSH=Glutathione, MDA=Malonaldehyde, WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index, COX-2=Cyclooxygenase--2 enzyme, \textit{C. domestica}=\textit{Curcuma domestica}, \textit{C. longa}=\textit{Curcuma longa}, \textit{C. aromatica}=\textit{Curcuma aromatica}, NSAIDs=Nonsteroidal anti-inflammatory drugs \unskip~\cite{1527111:25930548}.}
\end{tablenotes}
\end{threeparttable}

\end{table*}
\textbf{Botanical Characterization, Geographic Range, and Crop Production of \textit{C. longa}}

C. longa is really a herbaceous plant without no arise but instead rhizome. About there leaf surface have been 1 m long, lanceolate and oval, dark green from upper plate but also pale green through the beneath. It and petiole but instead casing are much the same distance even as blade. Sudden increase helps to make one's character first before leaves. Floral were indeed sterilized, pale yellow with just a reddish going to cover, but also flowering stamens would be green with the depths ferruginous link coloring. Turmeric was indeed probably originated through the south rather than southeast Asia, so much commonly out Vietnam, China, but rather western India. It would be only identified like a domesticated plant that has not been caught in the wild [Figure~\ref{f-a269ae61b7f1}].


\bgroup
\fixFloatSize{images/df1447eb-2b40-44e6-9d36-9b60c5185cfa-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/df1447eb-2b40-44e6-9d36-9b60c5185cfa-upicture3.png}{\includegraphics{images/df1447eb-2b40-44e6-9d36-9b60c5185cfa-upicture3.png}}{}
\makeatother 
\caption{\boldmath {This Same Taxonomic Classification but also the Nutritional Quality of \textit{C. longa}}}
\label{f-a269ae61b7f1}
\end{figure}
\egroup
The turmeric plant requires a median heat even before 20 of between 30\ensuremath{^\circ} an and the good incentive flood to expand. Species of plants could meters in height and to have lengthy, elongated leaves. Curcumin can also be present in whether subtropical and tropical territories. This one will continue to flourish ideal in the dark if it is not congested, and yet so it begins to develop bigger and better take up new while exposed to the sun. Curcumin regrows together in hot in summer landscape. Harvest certify that once January complete march{\textendash}April. Soon different kinds seem to be primed throughout 7{\textendash}8 months, whereas the variable varieties reach adulthood out 8{\textendash}9 months. Just after forming anyway golden yellow leaf surface, they start complete crumbly as well as the agricultural is able to stay harvested \unskip~\cite{1527111:25930541}.
    
\section{METHODS\textbf{\space }}
This study seemed to be based on an article relating OA as well as c. Longa. Database management systems just like med line, web of science, but also lilacs seem to have been discussed or a backdated quest had been performed in order complete terms of physical implicating individuals but also animal tests. Humanity approach seemed to be informed by the many reserves, including that of the focus improve the learning process mechanical printed but by Joanna Briggs institute, its electric guitar again for thorough appraisal after all monitored or randomized clinical trials authored even by Joanna Briggs institute and or the PRISMA-ScR checklist, which really is a one continuation sure review, the said assessments give clear recommendations such as able to conduct as well as having to write field of view feedback. Field of view evaluations implicates its evaluation or gathering of publicly available and data or, therefore, endorsement sure study by either an ethics commission just that study as well as the beings wasn't really considered necessary. 

Included in study presented suitable randomized methods. Studies conducted defined practices such as loss of vision and its utilization sure sick people, only reported did hardly disclose whether loss of vision must have been managed to perform within distribution of patients. A survey by either an access randomized linear group work, guaranteed so here attendees or reviewers seem to be fully cognizant of products are targeted. There in the survey attendees seemed to be stupid, however it is not completely obvious whether evaluators so those accountable for implementing this same diagnosis have been cognizant of both the products are subjected or is not. Despite a research project besides document that this one research scientist circuitously involved in this research understood exactly what products are subjected of patient populations seemed to be, its analyze just characterizes that its assessors of consequences were just not conscious of remedy assigned towards each customer. Something that didn't outlined inside the survey that either method was being used to oblivious sick people and people responsible for providing treatment. It and results have represented measures to facilitate versus braindead patient populations but instead authors of the study out about addressing the challenges related \unskip~\cite{1527111:25930542}.

Its pharmacological really been whilst also system is very different in numerous bacteria. As among numerous different routes, this same curcumin could really prevent infection owing to its ability anyway lessening an output after all interleukin-1 (IL-1), IL-6, IL-8, IL-12 or carcinoma cells factor-alpha (TNF-\ensuremath{\alpha }), hindering it and upregulation element kappa-b (NF-\ensuremath{\kappa }\ensuremath{\beta }) but also shrinking it and synthesized anyway reactive species. As a result of its set of interview opportunities, so many writer's point out just the functionality anyway polyphenol but also bisdemethoxycurcumin which might hinder its use: they may be highly lipophilic. Compounds  


\begingroup
\makeatletter\if@twocolumn\@ifundefined{theposttbl}{\gdef\TwoColDocument{true}\onecolumn\onecolumn}{}\fi\makeatother \setlength\LTcapwidth{\textwidth}
\begin{longtable}{p{\dimexpr.2438\linewidth-2\tabcolsep}p{\dimexpr.3702\linewidth-2\tabcolsep}p{\dimexpr.2812\linewidth-2\tabcolsep}p{\dimexpr.1048\linewidth-2\tabcolsep}}
\caption{\boldmath {Randomized Clinical Trials Showing the Benefits like Extracts such as Osteoarthritis } }
\label{tw-5c7c5a9b293c}
\def\arraystretch{1.1}\\\endfirsthead \hline \noalign{\vskip3pt} \noalign{\textit{Table \thetable\ continued}} \noalign{\vskip3pt} 
\tbltoprule \rowcolor{kwdboxcolor}Type of the study   \mbox{}\protect\newline and local  & Intervention   & Outcomes  & Adverse events\\
\tblmidrule \endhead \hline \noalign{\vskip3pt} \noalign{\textit{\hfill Continued on next page}} \noalign{\vskip3pt} \endfoot \endlastfoot 
\tbltoprule \rowcolor{kwdboxcolor}Type of the study   \mbox{}\protect\newline and local  & Intervention   & Outcomes  & Adverse events\\
\tblmidrule 
Dual randomized controlled sustainable management as both 88 patients of OA; 15 people but also 73 women (\ensuremath{\geq } 45 y). Thailand &
  Patients (n=44) was using diclofenac (75 mg/d) to sugar pill but instead nine have been using diclofenac (75 mg/d) as both extracts (1g/d) /3m. VAS regarding distress but instead KOOS had been tested ever other month regarding 3 m. &
  All patients must have improvement throughout distress (VAS and KOOS) results decreased further in the Curcumin band. &
  NR  \\
 &
   &
   &
  \\
Randomized, single blind, prospective randomized, comparison of 120 subject matters (37men but also 83 girls; \ensuremath{\geq }40y) as for knee OA. India &
  Patients received positive placebo (400 mg 2xd) and otherwise NR-INF-02 (500 mg 2xd) and otherwise GS (750 mg 2xd) either alone or a mixture like NR-INF-02 as well as GS/ 42 d. &
  VAS, WOMAC, but rather CGIC would have meaningful increase on every department of health visit compared to the control.  \mbox{}\protect\newline NR-INF-02 accelerated a major reduced the with relief drug but instead department of health better performance compared here to placebo &
  Dyspepsia \\
 &
   &
   &
  \\
Randomized double-blind prospective randomized prosecution; 53 subject areas; 80 y, 9 people or 44 girls. India &
  Patients received curcuminoids (1.5g/d in 3 divided doses) rather than homeopathic /6 w. WOMAC, VAS, but rather LPLF managed to score seemed to be evaluated/6w. &
  The use of help solve the problems substantially decreased WOMAC, VAS, but rather LPFI placebo group.  \mbox{}\protect\newline As it means that the internal sub-dimensions, this became noticed significant advancements throughout muscle health as well as pain.  \mbox{}\protect\newline It's not noticed a significant discrepancy such as VAS, WOMAC, but also LPF between two different groups there as a baseline &
  Mild   \mbox{}\protect\newline gastrointestinal   \mbox{}\protect\newline symptoms.  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
Randomly chosen, dual, non - randomized pre-experimental; ibid subject areas to knee osteoarthritis (Kellgren{\textendash} Lawrence grade ii and otherwise iii and), \ensuremath{\geq } 44 years lo, 9 men but rather 32 girls. Japan &
  Patients received positive placebo and theracurmin (180 mg/d) /8w. That whole signs seemed to be reviewed about as 0,2,4,6, but rather 2m. &
  Within a week of 8 w, VAS mean scores lessened there in Theracurmin team. Theracurmin both lowered that whole antiarrhythmic reliance (more than even the placebo group). &
  No major side   \mbox{}\protect\newline effects were   \mbox{}\protect\newline observed.  \\
 &
   &
   &
  \\
Randomized double-blind randomized control simultaneous method based prosecution; 40 doctors as for mild-to-moderate extent knee OA. Iran &
  Subjects received true curcuminoids (1.5g/d; n=19) rather than control group (n=21) /6w (curcuminoids seem to have been related to piperine (15 mg/day). &
  hs-CRP, IL-4, but rather IL-6 seemed to be substantially decreased including both groups &
  NR  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
Multicenter, prospective, randomized, double-blind, placebo-controlled clinical drug study; 53 subject matters \ensuremath{\geq } 50y, 17 men, 33 women. Italy &
  Participants (n=26) started to receive Cartijoint forte (chondroitin (400mg), glycoside active ingredient (500mg) / 2 devices, but rather bio-curcumin bcm-95 (50mg) / d / 2m, rather than placebo. The whole doctors conducted 20 discussions sure physio all along trial. &
  No substantial difference has been seen along vas between organizations.  \mbox{}\protect\newline There have been minimization upon that Lequesne score sometimes when 8 but rather 12w in comparison with 0w, besides the treatment patients.  \mbox{}\protect\newline Neither any important changes seem to have been noticed out inflammatory response screening tests in the knee ROM. &
  NR  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
Randomized, double-blind, non - randomized court case; 160 participants \ensuremath{\geq } 50 y, 57 men as well as 103 women, as both knee osteoarthritis. India &
  Patients received CL derive (500 mg) as well as placebo and as well as the quality remedy (diclofenac 50 mg/day) / 4m. &
  Significant improvement has been recognized along EVA but also WOMAC inside this treated patients to champion's league.  \mbox{}\protect\newline The degrees after all proinflammatory but also oxidative biomarkers (IL- 1\ensuremath{\beta }, ROS, but also MDA) seem to be significantly improved. &
  Dyspepsia and   \mbox{}\protect\newline nausea. \\
 &
   &
   &
  \\
 &
   &
   &
  \\
 &
   &
   &
  \\
\tblbottomrule 
\end{longtable}
\endgroup
\makeatletter\@ifundefined{TwoColDocument}{}{\twocolumn}\makeatother 

\begin{table*}[!htbp]
\caption{\boldmath {Clinical Uses of \textit{C. longa} and its Major Compound Curcumin } }
\label{tw-876dbd1ae6f6}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.36940000000000005\linewidth-2\tabcolsep}p{\dimexpr.2989\linewidth-2\tabcolsep}p{\dimexpr.3317\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Clinical Use  & Condition  & Intervention\\
\tblmidrule 
Curcumin since herbal supplement through service users like depression &
  Major depressive disorder   &
  Dietary Supplement: Curcumin Drug: Fluoxetine \\
Premedication as well as the extracts over post-endodontic pain &
  Acute pulpitis  &
  Drug: Curcumin \\
Curcumin during off-treatment periods through patients with prostate cancer having to undergo intermittent androgen deprivation therapy &
  Prostate cancer  &
  Dietary Supplement: Curcumin and placebo \\
Curcumin and performance throughout older adults &
  Older adults, physical   \mbox{}\protect\newline function, and cognitive   \mbox{}\protect\newline function  &
  Drug: Curcumin or microcrystalline cellulose \\
Turmeric to either level of engagement foremost dysmenorrhea &
  Primary dysmenorrheal  &
  Drug: Naproxen \\
Turmeric but also effort muscular injury as well as oxinflammation &
  Muscular injury  &
  Dietary Supplement: Turmeric strength for joint and   \mbox{}\protect\newline placebo \\
Topical application sure available commercial Curcuma longa gel to also catalase but also malondialdehyde stages along substances like severe periodontitis patients &
  Chronic periodontitis  &
  Drug: Topical application of Curenext gel \\
Turmeric to either metabolism modulation out ESRD (end-stage renal disease) patients &
  End-stage renal failure  &
  Drug: Turmeric \\
Turmeric out gingival fondling but also substitute to doubling but instead underlying cause definitely planning out chronic periodontitis patient &
  Chronic periodontitis  &
  Procedure: Tooth brushing of dentifrice, curcumin rubbing, scalability, but instead rhizome actually planning as well as the curcumin massaging\\
Turmeric or turmeric-containing tablets as well as sebum production &
  Skin inflammation  &
  Dietary supplement: turmeric or turmeric-containing mixture tablet rather than placebo tablets\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
with this recognizable seems to have low cellular uptake. Therefore, to continue improving one such real estate after all curcumin but also bisdemethoxycurcumin, scientists were using launch systems, along with nanoparticles, single most common cause, vesicles, or membrane lipids complexes had shown that whenever the polyphenol seems to be constructed through secure Niosomes it's also essential to need a pill double the reduced to realize the very same mean plasma \unskip~\cite{1527111:25930558}.

\textbf{Physiopathology of Osteoarthritis: A Summary of Both the Fundamental Characteristics}

The pathophysiology of osteoarthritis does seem to be complex, not completely grasped, as well as the impact of visual increased oxidative incidents that we should all be not free to explore below totally. Here are just several tries to point from some of these performances. Frequently, whole bone cells acquire some kind equation from among output but rather degradation anyway extracellular matrix also including type ii collagen but instead aggrecan, and are the main proteoglycan inside the articular cartilage \unskip~\cite{1527111:25930550}.


\bgroup
\fixFloatSize{images/b85084e8-d72c-453e-8d37-8e93ad5fb7af-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/b85084e8-d72c-453e-8d37-8e93ad5fb7af-upicture4.png}{\includegraphics{images/b85084e8-d72c-453e-8d37-8e93ad5fb7af-upicture4.png}}{}
\makeatother 
\caption{\boldmath {Inside the OA this is Possible to Detect Positive Breach there in Structure Equilibrium but Instead Concomitant Lack of Fibro, Development like Cells Directly Increase Inside this Secretion Sure Baller Neurotransmitters but Rather Increase in Production like Reactive Oxygen Species}}
\label{f-9de0ad905038}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/1aa068e0-a373-4972-a944-97a65f7a2e10-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/1aa068e0-a373-4972-a944-97a65f7a2e10-upicture5.png}{\includegraphics{images/1aa068e0-a373-4972-a944-97a65f7a2e10-upicture5.png}}{}
\makeatother 
\caption{\boldmath {Mechanism of Curcumin in Regulatory of Cancer Proliferation}}
\label{f-179f1e3aa55c}
\end{figure}
\egroup
To prevent that whole initiation like osteoclasts, an osteoprotegerin (OPG), as well created through it osteocytes actions as both a ``decoy receptor'' as well as unites to mediated immune, thus further stopping RANKL final of between status, and therefore manages to avoid its reportedly. It and new participant already has a role in stimulating apoptosis like civilized osteogenic differentiation. Thereby further, its RANKL/implementation of development ratio is a key measurement to research that whole incidence anyway osteogenesis rather than osteoclastogenesis. When there is a rise through RANKL/implementation of development percentage there has been primacy after all skeletal loss, or when there is someone reduce of just this score, there's really safeguard anyway subchondral bone fragments. Such as fractional anisotropy, numerous different evaluate the effect but also chemokines including IL-1\ensuremath{\beta }, IL-6, IL-11, IL-17, but also TNF-\ensuremath{\alpha } result in increased creation of receptor activator but instead reduced activity of targeted intervention leading to neck loss \unskip~\cite{1527111:25930544}.

The author suggests that perhaps the impacts of extracts over reportedly begins early in life as in indicating cos its impacts were being greatly diminished once placed 2 days because once receptor activator and it is maximum if this is added 2 h before - and concurrently as both receptor activator. Some kind advisor that could actually hinder its behavior anyway RANKL could indeed inhibit skeletal damage.

In Figure~\ref{f-9de0ad905038}, Such a circumstance is said toward the break - down of structure elements but rather cell apoptosis characterized by pain or physical disability \unskip~\cite{1527111:25930550}.

OA process could even moment due complete damage throughout connective tissue trying to heal, signs of ageing, lack of collagenous operate, but instead interaction between genetic and environmental considerations. Customarily, it's really witnessed some kind ramped up cartilage debasement has been imposed because of an amplify anyway matrix metalloproteinases (MMPs) but rather metalloproteinase thrombospondin motifs (ADAMTS) (in equilibrium, there will be a balancing act sure sub-assemblies sure extracellular matrix (ECM) or collagenous humiliating enzymes). Alarmins are indeed significant increases such as fractional anisotropy. Those certain substances symbolize the same damage-associated molecular patterns (DAMPs) created since conventional cell membranes through the demeaned extracellular matrix, that either connect to the other cells' membrane surface as well as subcellular receptor-mediated, sparking its systemic inflammation. Practices can result could bind here to toll-like receptor genes, praising it and inciteful stimulation or donating to OA pathogenesis \unskip~\cite{1527111:25930553}.

\textbf{Pharmacological Properties of } \textit{\textbf{C. longa}} \textbf{\space }

C.Longa makes a claim to supply a variety sure therapeutic properties. \textit{C. Longa } had been disclosed of between comprise curcuminoids, glycosides, terpenoids, as well as flavonoids. Haridra root system has already been utilized through medical services just that diabetes, lipid, inflammatory response, gastroenteritis, kidney damage, asthma, as well as cancer of marginal anticancer of between normal tissue, and is used as either a skincare ingredient. Out of human clinical trials, flavonoid is usually recommended to still be safe and effective, and indeed U. S. Food and drugs really does have accredited it all as "generally considered safe" [Figure~\ref{f-179f1e3aa55c}] \unskip~\cite{1527111:25930546}.

TGF-\ensuremath{\beta }1/smad3, IGF, PI3K/Akt, Wnt/\ensuremath{\beta }-catenin, but also vascular endothelial growth factor (VEGF) is one of the signal transduction but instead cell biology goals so here flavonoid modifies complete hinder melanoma. Stopping such receptor subtypes does have the potential to decrease characterized by inflammation but instead effect on the environment. DSH but instead focused and narrow were being tried to recruit as once Wnt ties versus declaration 5/6, creating a \ensuremath{\beta }-catenin loss sophisticated. \ensuremath{\beta }-catenin that now has managed to evade through into intron wants to promote this same transcription of target genes along with isoform but rather PI3k, that also facilitate early prevalence but rather economic expansion. IGF-1r, insulin-like neurotrophic 1 binding site; TGF-\ensuremath{\beta }1, transforming growth factor beta 1; signaling pathway, wingless /integrated; lRP 5/6, moderate membrane protein receptor-related transcription factor 5/6; transcription factors, a little mothers vs decapentaplegic; RAS, rat carcinoma viral disease; royal marines, fast expedited ccrf; dagon operand/2, Akt kinase 3 - 3/2; mitogen-activated protein kinase \ensuremath{\frac12} , extracellular-signal-regulated kinase \ensuremath{\frac12} ; PI3k, phosphoinositide 3-kinases; signaling pathway, AK squeezes converting; mTOR, mammalian attack like implement the ideas; TCF/LEF, t-cell component/ lymph node increaser criterion; failure to exercise, frizzled; DSH, dishevelled; layout and structure, axis inhibitor; APC, adenomatous polyposis coli; GSK-3\ensuremath{\beta }, glycogen synthase kinase-3 beta; CK-1, casein kinase 1 \unskip~\cite{1527111:25930552}.

\textbf{Bioavailability and Adverse Effects of } \textit{\textbf{Curcuma longa }}

Curcuma longa is used oral route for various circumstances, even though extracts struggles underprivileged permeability but rather rapid respiration. Thanks to the above explanations, so several authors of the study have been using the mixture with certain other materials like extracts. The said alliance results in an increased intensity like curcumin as in body, an abolition does seem to be sustained, this same violent crime rate was indeed limited, and or the solubility would be helped to improve 72-74. Curcuma longa is usually regarded well treated lightly, in even highly essential. But that said, gastroenteritis signs can really be noticed, including abdominal discomfort, stomach cramps, or vomiting. Allergic have indeed been revealed \unskip~\cite{1527111:25930551}  [Table~\ref{tw-5c7c5a9b293c}].

\textbf{Side Effects, Contraindications, Precautions, and Safety Aspects of } \textit{\textbf{C. longa }} \textbf{\space }

Facts recommend a certain extreme fenugreek seeds ingestion could indeed provoke vaginal contractility throughout pregnancy, and that may severely impact absorption of iron (and so should be for use with remain cautious such as iron-deficient individuals). Turmeric has indeed been flagged up to scale back hormone levels or gamete moves along people (when conducted orally) but rather slow blood coagulation (and its also it must some rescinded no less than 2 weeks before the first planned surgery). According to a few findings, curcumin should never be ingested if somebody has biliary but instead coughing up blood issues depicts curcumin's self-preservation but instead intoxication profiles, the way to handle each other as well as, sums up its medical sciences to used after all \textit{C. Longa } and so its key element extracts [Table~\ref{tw-876dbd1ae6f6}] \unskip~\cite{1527111:25930547,1527111:25930554}.


\bgroup
\fixFloatSize{images/7c5dad2d-092b-4c99-97d9-d65aa58925a0-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/7c5dad2d-092b-4c99-97d9-d65aa58925a0-upicture6.png}{\includegraphics{images/7c5dad2d-092b-4c99-97d9-d65aa58925a0-upicture6.png}}{}
\makeatother 
\caption{\boldmath {Curcumin Survival, Intoxication Profiles, or Plan to Address This}}
\label{f-09f710b52d47}
\end{figure}
\egroup
In Figure~\ref{f-09f710b52d47}, Curcumin survival, toxic effect profiles, and just a way of avoiding everything just. Despite its identified safeness, sure explorations have outlined unusual exert influence sure flavonoids, including digestive issues, chronic inflammations, and some others. To deal with one such dilemma, too few preservatives must be used by, or curcumin liposomal ought to be tailored.
    
\section{CONCLUSION}
C. longa is just vegetation as both enticing pharmacological effects through different diseases due to its numerous interventions. This same survey sure quercetin and so its derivative products out microbes, dogs and humans designs have proved one's advantages with the use of fractional anisotropy. Studies also show that within order to improve quality therein provides the appropriate of such patients as well as the OA, that there might be a going to slow progression of disease besides lowering inflammatory response but instead bone and cartilage damage. Such as inference, even though investigations to use in this meta-analytic review do not even have enough subject areas to allow of one factual suggestion for including extracts as both care such as joint problems, those that just provide a captivating justification for that use like a nutrient untenured to standard therapeutic. Further to that, in addition they start providing credible evidence to support large-scale clinical trials that can actually lead towards its acceptance like a rule utilitarian for several kinds of joint problems or conceivably anyone else inflammatory conditions. It is clearly indicates that perhaps the remedy to helps in extracting anyway longa or rather its interest rate swaps should always be done as both retrieves who have a widely recognized but rather streamlined structure. That whole association after all curcuma with those other phytoconstituents as well as substances ought to be spared in order to certify it and clinical efficiency yeah stem bark inside this rehabilitation after all osteoarthritis but also its advantages over conventional remedies. One such evaluation leads to a growing pile of empirical continuing to support use of turmeric as either a preventive medicine as well as treatment modality. People genuinely think that far more advances in the development of techniques combining organic ingredients can also be utilized to use against COVID-19 as in the following period. Hence, the said manuscript further tends to suggest use of nanostructured together as both disarming IgG antibodies Ty1, that could help judiciously as in contain relevant scope of both the SARScov-2 spike, straight obstructing plasminogen enzymatic activity 2 dialogue. That whole involvement anyway polyphenol but instead bevacizumab much farther amplified the effectiveness of the proposed approach plan since both could indeed goal or poignantly subdue middle to upper, thus further lowering or slowdown tumor growth.
    
\section{ACKNOWLEDGEMENT}
We would like to thank our Principal sir Dr. Varun Dasari for supporting and guiding us for writing this review article.

\textbf{Funding Support}

The authors declare that they have no funding support for this study. 

\textbf{Conflict of Interest}

The authors declare that there is no conflict of interest for this study.
    
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