Concurrent, New-Onset Autoimmune Hepatitis, Celiac Disease, and Hashimoto's Thyroiditis Following COVID-19: A Case Report.

Here we describe a 13-year-old adolescent female diagnosed with concurrent autoimmune disorders including Grave disease, Celiac disease, and autoimmune hepatitis within 3 months after infection with severe acute respiratory syndrome coronavirus 2. The patient initially presented to her pediatrician with complaints of epistaxis, cessation of menses, palpitations, and weight loss. Initial evaluation showed evidence of hyperthyroidism, elevated liver enzymes, and abnormal Celiac disease serologies. Additional testing including laboratory tests, liver biopsy, and an upper endoscopy with biopsies confirmed the diagnosis of Grave disease, Celiac disease, and type 1 autoimmune hepatitis. This case highlights the importance of recognizing the risk of autoimmune disorders associated with the novel coronavirus disease 2019.

Natural 3D Extra Cellular Matrix mimicking stem cells seeded decellularized scaffolds as a platform for tendon regeneration.

Achilles tendon, which connects the calf muscles to heel, is the strongest tendon in the body. Despite its strength, it is more prone to injury due to its limited blood supply. Tendon-related injuries are more common in sportspersons, people with labor-intensive work and the aged community. The currently available treatment mode is surgery which is expensive with chances of re-injury. Present study made an attempt to fabricate a tissue-engineered tendon product using decellularized tendon (DT) seeded with stem cells and bioactive components of Tinospora cordifolia extract (TCE). The bare DT tissue scaffold/substitute may also serve as a drug delivery platform for growth factors and cells with a new approach to promote tissue regeneration in clinical applications. DT construct showed good regenerative potential and easily promoted new tissue formation. Decellularization of the tendon was carried out by chemical method using tri (n-butyl) phosphate (TnBP). DT was physicochemically characterized by contact angle measurement, thermal gravimetric analysis (TGA), and mechanical testing. Rabbit adipose derived mesenchymal stem cells (RADMSCs) were isolated and phenotypically characterized by flow cytometry analysis, tri lineage differentiation, and so forth. Further, stem cell seeded DT scaffolds were prepared and found to be non-toxic by cytotoxicity, cell adhesion by scanning electron microscope (SEM) analysis, cell viability by live dead assays, and so forth. The findings of this study yield valid proof for the employability of cell-seeded DT construct as a natural scaffold in repairing injured tendons-the toughest chords of the skeleton. This is a cost effective method for the replacement of injured/damaged tendons for athletes, people in labor-intensive occupations, the elderly population, and so forth-a boon towards the repair of the tendon in damage/injury.

Neural Tissue Engineering with Rat Adipose-Derived Mesenchymal Stem Cells: The Role of an Injectable, Resorbable Hydrogel Scaffold Derived from Oxidized Alginate and Gelatin.

The central nervous system has limited regeneration potential. The multipotency of adipose-derived mesenchymal stem cells (ADMSC) makes them an ideal autologous cell source for the regeneration of neural tissues. However, the likelihood of their differentiation into unwanted cell lineages when transplanted into a hostile injury environment is a serious disadvantage. Transplanting predifferentiated cells via an injectable carrier may aid in site-specific delivery for better survival of cells. Here, we focus on identifying an appropriate injectable hydrogel system that favors stem/progenitor cell attachment and differentiation for neural tissue engineering. An injectable composition of the hydrogel, derived from alginate dialdehyde (ADA) and gelatin, was formulated for this purpose. This hydrogel promoted proliferation/differentiation of ADMSCs to neural progenitors, visualized from the generation of prominent neurospheres and stage-specific expression of a neural progenitor marker (nestin, day 4), an intermittent neuronal marker (ß-III tub, day 5), and a mature neuronal marker (MAP-2, day 8) with neural branching and networking (>85%). The differentiated cells also expressed the functional marker synaptophysin. There was no negative impact on stem/progenitor cell survival (>95%) or differentiation (∼90%) as compared to two-dimensional (2D) culture. Addition of appropriate quantities of asiatic acid specific for neural niche supported cell growth and differentiation without affecting cell survival (>90%) and improved neural branching and elongation. Optimized interconnected porous hydrogel niche exhibited rapid gelation (3 min) and self-healing properties mimicking native neural tissue. Both ADA-gelatin hydrogel by itself and that incorporated with asiatic acid were found to support stem/neural progenitor cell growth and differentiation and have potential applications as antioxidants and growth promoters upon release at the cell transplantation site. In short, the matrix itself or incorporated with phytomoieties could serve as a potential minimally invasive injectable cell delivery vehicle for cell-based therapies of neural diseases.

Primary Spinal Epidural Diffuse Large B-cell Lymphoma: Case Report and Literature Review.

Primary spinal epidural lymphoma (PSEL) comprises a group of tumors present only in the spinal epidural space with a histopathological picture of lymphoma and negative diagnostic workup for lymphoma at other sites. We present the case of an older male adult with primary spinal diffuse large B-cell lymphoma (DLBCL) presenting with spinal cord compression who was treated with surgery followed by high dose methotrexate in combination with RCHOP (rituximab, cyclophosphamide, prednisone, vincristine, and doxorubicin). This case report and review of literature on DLBCL limited to the spine provide a novel chemotherapy regimen and a comprehensive perspective on the optimal management of these patients.

3D-bulk to nanoforms of modified hydroxyapatite: Characterization and osteogenic potency in an in vitro 3D bone model system.

Synthetic bioceramics are replacing conventional methods of treating bone defects with autografts owing to the high demand of bone substitutes, with their Surface topography and size contributing to favor cytocompatibility in tissue regeneration. This experimental study deals with the comparative evaluation of the physical characterizations of four different in-house synthesized bioceramics from 3D-bulk to nanoforms of hydroxyapatite (HA), Biphasic calcium phosphate (BCP), Strontium doped hydroxyapatite (SrHA) and Silica coated hydroxyapatite (HASi) and also simultaneously evaluates adhesion, proliferation and osteogenic differentiation of rabbit adipose derived mesenchymal stem cells (RADMSCs) on these biomimetic ceramic niches. The osteogenic induced cells grown on 3D scaffolds for a period of 7, 14, 21, and 28 days were analyzed for their viability (MTT, LDH, live-dead assays), morphology (SEM), proliferation (Cytox-Red) and osteogenic differentiation (ALP, osteocalcin expression). Cellular activities and differentiation of RADMSCs were significantly higher on SrHA indicating the role of strontium in the differentiation of mesenchymal stem cells on this ceramic platform to the bone lineage. In order to reinforce the materials for hard tissue implantation and drug delivery, nano-SrHA (nSrHA) became the nanoparticle of choice based on its non-toxicity, cytocompatibility and osteogenic properties (nSrHA > nHASi > nBCP > nHA).

Capsanthin, a Plant-Derived Xanthophyll: a Review of Pharmacology and Delivery Strategies.

Capsanthin, a brightly orange-red-coloured pigment responsible for the peculiar red colour of paprika fruits (Capsicum annuum), belongs to xanthophylls, a class of oxygen-containing carotenoids. The characteristic chemical structure of capsanthin containing a keto group in conjunction with a long chain of 11 conjugated dienes is responsible for its strong radical scavenging and singlet oxygen quenching ability. Chemopreventive, antitumour, skin photo-protective, anti-inflammatory, and antidiabetic activities demonstrated by capsanthin are a consequence of its potent antioxidant action. Anti-obesity, anti-adipogenic, and antihyperlipidaemic activities are some of the more important features of capsanthin. With natural origin, bright red colour, and array of health benefits, capsanthin has a potential to be translated into a commercial cosmeceutical, nutraceutical, and/or pharmaceutical. However, the very low aqueous solubility of capsanthin is responsible for its highly variable and poor oral bioavailability. Moreover, its susceptibility to degradation due to heat, light, oxygen, and moisture poses challenges in the development of stable formulations for this otherwise meritorious compound. The current review presents various pharmacological activities of capsanthin and their underlying mechanisms. The review further discusses hitherto explored formulation strategies to improve solubility and stability of capsanthin. Graphical abstract.

Mesenchymal Stem Cells Seeded Decellularized Tendon Scaffold for Tissue Engineering.

Tendon is a collagenous tissue to connect bone and muscle. Healing of damaged/injured tendon is the primary clinical challenge in musculoskeletal regeneration because they often react poorly to treatment. Tissue engineering (a triad strategy of scaffolds, cells and growth factors) may have the potential to improve the quality of tendon tissue healing under such impaired situations. Tendon tissue engineering aims to synthesize graft alternatives to repair the injured tendon. Biological scaffolds derived from decellularized tissue may be a better option as their biomechanical properties are similar to the native tissue. This review is designed to provide background information on the current challenges in curing torn/worn out the tendon and the clinical relevance of decellularized scaffolds for such applications.

Image-guided Fine Needle Aspiration Cytology of Intrathoracic Lesions.

BACKGROUND: Percutaneous, image-guided transthoracic fine needle aspiration cytology (TTFNAC) is a rapid, yet accurate, and well-established diagnostic method used in the cytological evaluation of intrathoracic lesions. The study was done to determine the utility of image-guided TTFNAC in diagnosis of intrathoracic lesions. SUBJECTS AND METHODS: A retrospective analysis of all cases who underwent image-guided TTFNAC of a suspected intrathoracic lesion, in a tertiary care hospital was done over a period of 3 years. RESULTS: During the study period, 124 cases of image-guided FNAC of intrathoracic lesions were obtained. The mean age at presentation was 60.5 years with M:F: 3.6:1. Neoplastic lesions (71.5%) outnumbered the nonneoplastic lesions (28.5%). The most common tumor was adenocarcinoma (25%) followed by squamous cell carcinoma (SCC, 11%), and small cell carcinoma (5%). There was one case each of anaplastic carcinoma, plasmacytoma, bronchoalveolar carcinoma, and non-Hodgkin lymphoma (NHL). Most of the lesions were found on the right side and upper lobe. Among the mediastinal lesions, we found two cases of thymoma and one case each of NHL)/primitive neuroectodermal tumor (PNET), NHL, and small cell carcinoma metastasis to lymph node followed by ten cases of inflammatory lesions and seven cases of tuberculosis (TB). CONCLUSION: Image-guided TTFNAC of intrathoracic lesions is a safe method when done by well-trained medical personnel with lesser rate of complications. An early accurate diagnosis of malignancy can be made based on the cytological features; however, further subtyping of the malignancy may sometimes be difficult due to overlapping cytological features. TTFNAC can be a diagnostic tool for identifying nonneoplastic lesion such as TB. Hence, image-guided FNAC aids in early diagnosis and management of patients with intrathoracic lesions.

Novel flourescent spiroborate esters: potential therapeutic agents in in vitro cancer models.

The current treatment system in cancer therapy, which includes chemotherapy/radiotherapy is expensive and often deleterious to surrounding healthy tissue. Presently, several medicinal plants and their constituents are in use to manage the development and progression of these diseases.They have been found effective, safe, and less expensive. In the present study, we are proposing the utility of a new class of curcumin derivative, Rubrocurcumin, the spiroborate ester of curcumin with boric acid and oxalic acid (1:1:1), which have enhanced biostability for therapeutic applications. In vitro cytocompatibility of this drug complex was analysed using MTT assay, neutral red assay, lactate dehydrogenase assay in 3T3L1 adipocytes. Anti tumour activity of this drug complex on MCF7 and A431 human cancer cell line was studied by morphological analysis using phase contrast microscopy, Hoechst staining and cell cycle analysis by FACS. To explore the chemotherapeutic effect, the cytotoxic effect of this compound was also carried out. Rubrocurcumin is more biostable than natural curcumin in physiological medium. Our results prove that this curcumin derivative drug complex possess more efficacy and anti-cancer activity compared with curcumin. The findings out of this study suggests this novel compound as potential candidate for site targeted drug delivery.

Mutant cartilage oligomeric matrix protein (COMP) compromises bone integrity, joint function and the balance between adipogenesis and osteogenesis.

Mutations in COMP (cartilage oligomeric matrix protein) cause severe long bone shortening in mice and humans. Previously, we showed that massive accumulation of misfolded COMP in the ER of growth plate chondrocytes in our MT-COMP mouse model of pseudoachondroplasia (PSACH) causes premature chondrocyte death and loss of linear growth. Premature chondrocyte death results from activation of oxidative stress and inflammation through the CHOP-ER pathway and is reduced by removing CHOP or by anti-inflammatory or antioxidant therapies. Although the mutant COMP chondrocyte pathologic mechanism is now recognized, the effect of mutant COMP on bone quality and joint health (laxity) is largely unknown. Applying multiple analytic approaches, we describe a novel mechanism by which the deleterious consequences of mutant COMP retention results in upregulation of miR-223 disturbing the adipogenesis - osteogenesis balance. This results in reduction in bone mineral density, bone quality, mechanical strength and subchondral bone thickness. These, in addition to abnormal patterns of ossification at the ends of the femoral bones likely contribute to precocious osteoarthritis (OA) of the hips and knees in the MT-COMP mouse and PSACH. Moreover, joint laxity is compromised by abnormally thin ligaments. Altogether, these novel findings align with the PSACH phenotype of delayed ossification and bone age, extreme joint laxity and joint erosion, and extend our understanding of the underlying processes that affect bone in PSACH. These results introduce a novel finding that miR-223 is involved in the ossification defect in MT-COMP mice making it a therapeutic target.

Inhibition of LPS induced pro-inflammatory responses in RAW 264.7 macrophage cells by PVP-coated naringenin nanoparticle via down regulation of NF-κB/P38MAPK mediated stress signaling.

BACKGROUND: Naringenin (NAR) was found to display strong pharmacological properties. Since the clinical relevance of NAR is limited by its low bioavailability, we effectively synthesized and characterized a novel PVP-coated NAR nanoparticle (NAR NP) to enhance the therapeutic efficacy of NAR. The present study was designed to investigate the effects of NAR NP on lipopolysaccharide (LPS) induced inflammatory response in RAW 264.7 macrophage cells. METHODS: In vitro cell culture studies of LPS stimulated RAW 264.7 macrophage cells were used as experimental model. RESULTS: Cytotoxicity studies revealed that NAR NP is safe even at maximum tested concentration of 200µg/ml. Initial dose fixation study in LPS induced RAW 264.7 cells, revealed the minimum optimal concentration required for anti inflammatory effect as 25µg/ml. mRNA expression studies showed that NAR NP significantly down regulated the expressions of NF-κB and P38MAPK, which is paralleled with the inhibition of the nuclear translocation of NF-κB. This in turn led to the blockade of iNOS and COX-2, thereby inhibiting the production of nitric oxide and pro inflammatory cytokines such as TNF-α, IL-6, MCP-1 and IL-1ß. NAR NP was found to be more efficient, when compared with NAR. CONCLUSIONS: Anti-inflammatory effects of NAR NP may be allocated to the down-regulation of COX -2 and iNOS via the suppression of NF-κB and MAPK signaling pathway in RAW 264.7 macrophages. The data suggests that NAR NP can be used as a potent candidate for the treatments of inflammatory diseases by exploiting the nanoscale properties and targeting efficacy.

Photodynamic therapeutic efficacy of symmetrical diiodinated squaraine in in vivo skin cancer models.

BACKGROUND: Photodynamic therapy (PDT) has clinical approval for use as a minimally invasive therapeutic procedure that is able to exert selective cytotoxic activity toward malignant cells. The dye selected for our study, symmetrical diiodinated squaraine, is one of the newly developed photosensitizers. The study is designed to determine the efficacy of PDT mediated by symmetrical diiodinated squaraine in skin tumor induced Swiss albino mice. METHODS: Skin tumor was induced in mice with dimethyl benzanthracene (DMBA) and croton oil. After squaraine administration to the tumor mice, photodynamic treatment of tumors was performed using a 1000W halogen lamp corresponding to the light dose of 100J/cm2. The mice were euthanized and skin flaps and tumor tissues from the back of mice were excised for biochemical studies. The biochemical parameters analyzed include some relevant tumor markers for epithelial tissues, inflammatory markers and markers of apoptosis. The gene expression studies were done by RT-PCR. RESULTS: After two weeks of the treatment, there was significant inflammation. However at 90days after PDT, the parameters reverted to near-normal values. All marker parameters of tumor progression brought back to normal levels by PDT. Increased caspase-3 activity in PDT treated group shows that cell death might have occurred by apoptosis. The gene expression profile confirms the results. CONCLUSIONS: The results of the whole study show the therapeutic efficacy and apoptosis mediated tumor destruction by squaraine PDT.

A Novel Fluorescent Quantum Dot Probe for the Rapid Diagnostic High Contrast Imaging of Tumor in Mice.

A simple probe - antibody conjugated silica over coated cadmium selenide quantum dots (QD-Ab probe) for efficient and rapid diagnostic in vivo imaging of tumors is developed. Compared to unconjugated quantum dots (QD), these probes underwent efficient cellular internalization and tumor targeting behavior, retaining bright emission under in vivo cancer models. Silica over coated cadmium selenide quantum dots were conjugated with Epidermal growth factor receptor (EGFR) monoclonal antibody to detect the over expression of EGFR in cancer models. The in vitro cellular internalization efficiency of QD and QD-Ab probe in cultured stem cells (RADMSCs) and cancer cells (HeLa) were assessed by ICP-OES and cLSM. Results demonstrated a greater internalization efficiency of CdSe-Silica QD-Ab probe than CdSe-Silica QDs. For in vivo imaging solid tumor bearing mice was subjected to tail vein injection of QD and QD-Ab probe. After the specific time interval of injection, mice were anesthetized and subjected into Xenogen IVIS®200 imaging system, followed by ex vivo imaging. Subsequently, ultrathin sections of tumor were imaged by using cLSM. Both in vivo and ex vivo imaging results confirmed the tumor-targeted imaging efficiency of QD-Ab probes compared to unconjugated QDs.

PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations.

Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.

Polyphenols of Cassia tora leaves prevents lenticular apoptosis and modulates cataract pathology in Sprague-Dawley rat pups.

Cataract is a leading cause of visual impairment worldwide with multifactorial etiology and is a significant global health problem with increasing prevalence with age. Currently, no pharmacological measures are discovered to prevent and treat cataract and a significant number of epidemiological studies have suggested the potential role of antioxidants in the prevention of cataract by scavenging free radicals and preventing lens protein derangement and lenticular cell damage. The main goal of the present study is to evaluate Cassia tora leaves; an edible leafy vegetable employed in Ayurvedic and Chinese system of medicine for eye rejuvenation in preventing selenite-induced cataract in rat pups and to identify the active components that produce the effect. ECT pre-treatment effectively restored both enzymatic and metabolic antioxidant levels, membrane integrity and reduced metal accumulation and thus down-regulate epithelial cell death. Gene expression studies also confirmed these findings. ESI-MS analysis of ECT revealed the presence of chrysophanol, emodin, kaemferol, quercetin, stigmasterol and isoquercetin. The study suggests the possible role of C. tora in alleviating cataract pathology and presence of many anthraquinones and flavonoids. As it is an edible plant, the incorporation of these leaves in daily vegetables might prevent or delay the onset and maturation of cataract.

Anthraquinones and flavonoids of Cassia tora leaves ameliorate sodium selenite induced cataractogenesis in neonatal rats.

The present study was undertaken to evaluate the efficacy of Cassia tora leaves, an edible plant traditionally used for eye ailments, in preventing experimental cataractogenesis. Cataract is the leading cause of irreversible visual impairment worldwide characterized by the cloudiness or opacification of the lens due to the disturbance of even distribution of lens proteins and lipids. A significant number of epidemiological studies have suggested the potential role of herbal medicine in the prevention of cataract by maintaining lens architecture. The study was conducted in neonatal rat pups of 8-10 days old with an ethyl acetate fraction of Cassia tora leaves (ECT) administered by gastric intubation. After 30 days, the animals were sacrificed and various parameters such as redox status and gene expressions were evaluated in lenses. ECT administration caused a significant decrease in the onset and maturation of cataract, potentiated antioxidant defense and normalized lens crystallin expression against cataract induced animals. HPLC and ESI-MS analysis of ECT revealed the presence of flavonoids and anthraquinones. Thus, the present study indicates the therapeutic potential of Cassia tora leaves in preventing cataract and the effect is endorsed by the presence of antioxidants in Cassia tora leaves.

Cassia tora leaves modulates selenite cataract by enhancing antioxidant status and preventing cytoskeletal protein loss in lenses of Sprague Dawley rat pups.

ETHNOPHARMACOLOGICAL RELEVANCE: Cataract is the clouding or opacity that develops in the eye's lens and is considered to be an unavoidable consequence of aging due to irreversible lens damage. Free radicals and oxidant species are reported to be the major factor responsible for the onset and pathology of cataract. No pharmacological measures are formulated to treat cataract blindness and surgical removal of the opaque lens is the only remedy till date. Boosting of antioxidant potential of the lens is proved to prevent cataract and many indigenous plants have been screened for anticataractogenic potential in the last decades. The objective of the present study was to determine whether Cassia tora leaves; the plant employed in traditional medicine for eye rejuvenation and ailments, can prevent cataract in neonatal rats. MATERIALS AND METHODS: Cataract was induced by a single subcutaneous injection of sodium selenite at a dose of 4 µg/g body weight on the 10th day and Cassia tora leaves was administered orally from 8th day upto 12th day at a concentration of 5 µg/g body weight. After 30 days; lens morphology, oxidant-antioxidant equilibrium, glutathione metabolism, cytoskeletal protein/gene expressions were monitored. RESULTS: Lens morphology, biochemical analysis and expression studies supported the anticataractogenic effect of Cassia tora leaves. CONCLUSION: In summary, it can be suggested that the consumption of these leaves afford protection to the lens with its antioxidant action and seems to be a new therapeutic approach against cataract by preventive protection.

Lupeol, a pentacyclic triterpenoid isolated from Vernonia cinerea attenuate selenite induced cataract formation in Sprague Dawley rat pups.

This study investigated the inhibitory effects of active component isolated from flavonoid fraction of Vernonia cinerea (FVC), lupeol on selenite induced cataract formation. Previous reports suggest that phytochemicals or natural plant products retard the process of cataractogenesis by scavenging free oxygen radicals. Hence, the present study sought to assess the potential of lupeol on in vivo selenite induced cataract models. Lupeol, a pentacyclic triterpenoid, was isolated from the ethyl acetate fraction of methanolic extract of Vernonia cinerea, follows standard chromatographic techniques. Structural elucidation of the compound was carried out using (1)H NMR, (13)C NMR, Mass spectrometry together with other complementary techniques (UV and IR). From these, the isolated compound was identified as Lupeol (3'-hydroxylup-20(29)-ene). The antioxidant activity was comparatively studied using DPPH radical scavenging and FRAP assay. Lupeol exhibited higher DPPH radical scavenging activity as well as reducing power assay. In this study, cataract was induced by a single subcutaneous injection of sodium selenite (4 µg/g body weight) on rat pups. Lupeol was administered orally from 8th day upto 21st day at a concentration 25 µg/g body weight. Cataract was visualized on 16th day with the help of an ophthalmoscope and later on with the naked eye. On the 30th day, rats were euthanized by sodium pentothal injection, lenses were excised and the biochemical parameters such as activity of superoxide dismutase (SOD), catalase (CAT), Glutathione peroxidase (GPx), Glutathione reductase (GR), Glutathione-S-transferase (GST), Ca(2+) ATPase, glutathione content (GSH), reactive oxygen species (ROS), lipid peroxidation products (malondialdehyde) were estimated and found effective in the treatment of cataract by lupeol.

Embelin (2,5-Dihydroxy-3-undecyl-p-benzoquinone) for photodynamic therapy: study of their cytotoxicity in cancer cells.

Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agent for the treatment of malignant tumor. The present study was carried out to evaluate the photosensitizing potential of embelin isolated from Embelia ribes. For PDT study, cells were grouped into four groups. Two types of control were used, one with Ehrlich's ascites carcinoma (EAC) cells alone (group 1) and one which received the illumination alone (group 2). Group 3 contains cells treated with different concentrations of embelin for 1 h at 37 °C. Another set of cells (group 4) after treatment with different concentrations of embelin was illuminated in ice for 4 min with a 1000-W halogen lamp. To study the mechanism of cell death, the following parameters such as reactive oxygen species (ROS), caspase-3, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS) were analyzed both in the absence and presence of light after the treatment of embelin. PDT study clearly indicated that embelin alone recorded no cytotoxicity, but for light treatment alone with the different concentrations of embelin, there was a significant induction of cytotoxicity in a concentration-dependent manner. Level of ROS and LDH increased in cells treated with embelin. Moreover, caspase-3 also increased which clearly indicated that cell death is through caspase-dependent apoptosis. This is the first report on PDT, a novel modality, using embelin for cancer therapy in vitro. The novelty of the study depends on the fact that cytotoxicity was produced by the synergistic effect of the embelin and light.

Embelin (2,5-dihydroxy-3-undecyl-p-benzoquinone): a bioactive molecule isolated from Embelia ribes as an effective photodynamic therapeutic candidate against tumor in vivo.

The present study was carried out to assess the photosensitizing potential of embelin, the biologically active natural product isolated from Embelia ribes in photodynamic therapy (PDT) experiments in vivo. In vitro PDT clearly indicated that embelin recorded significant cytotoxicity in Ehrlich's Ascites Carcinoma (EAC) cells, which is superior to 5-aminolevulinic acid, a known photodynamic compound. For in vivo experiments solid tumor was induced using EAC cells in the male Swiss albino mice of groups I, II, III and IV. Group I served as the control (without solid tumor), group II served as tumor bearing mice without treatment and groups III and IV served as treatments. At the completion of 4 weeks of induction, the tumor bearing mice from group III and IV were given an intraperitoneal injection with embelin (12.5mg/kg body weight). After 24h, tumor area in the Group III and IV animals was exposed to visible light from a 1,000 W halogen lamp. The mice from groups I to III were sacrificed 2 weeks after the PDT treatment and the marker enzymes (myeloperoxidase [MPO], ß-d-glucuronidase, and rhodanese) were assayed and expression of Bcl-2 and Bax were analyzed in normal and tumor tissues. Animals from group IV were sacrificed after 90 days of PDT treatment and the above mentioned parameters were recorded. Reduction in tumor volume and reversal of biochemical markers to near normal levels were observed in the treated groups. This is the first report on PDT using a natural compound for solid tumor control in vivo. The uniqueness of the mode of treatment lies in the selective uptake of the nontoxic natural compound, embelin from the medicinal plant E. ribes used in Indian system of medicine, by the solid tumor cells and their selective destruction using PDT without affecting the neighboring normal cells, which is much advantageous over radiation therapy now frequently used.