Tissue regeneration properties of hydrogels derived from biological macromolecules: A review.

The successful tissue engineering depends on the development of biologically active scaffolds that possess optimal characteristics to effectively support cellular functions, maintain structural integrity and aid in tissue regeneration. Hydrogels have emerged as promising candidates in tissue regeneration due to their resemblance to the natural extracellular matrix and their ability to support cell survival and proliferation. The integration of hydrogel scaffold into the polymer has a variable impact on the pseudo extracellular environment, fostering cell growth/repair. The modification in size, shape, surface morphology and porosity of hydrogel scaffolds has consequently paved the way for addressing diverse challenges in the tissue engineering process such as tissue architecture, vascularization and simultaneous seeding of multiple cells. The present review provides a comprehensive update on hydrogel production using natural and synthetic biomaterials and their underlying mechanisms. Furthermore, it delves into the application of hydrogel scaffolds in tissue engineering for cardiac tissues, cartilage tissue, adipose tissue, nerve tissue and bone tissue. Besides, the present article also highlights various clinical studies, patents, and the limitations associated with hydrogel-based scaffolds in recent times.

Recent updates on clinical developments of curcumin and its derivatives.

Curcumin, a natural polyphenol, derived from Curcuma longa L. is extensively studied by various researchers across the globe and has established its immense potential in the management of several disorders at clinical level. The underlying mechanism of curcumin involves regulation of various molecular targets, namely, inflammatory cytokines, transcription factor, apoptotic genes, growth factors, oxidative stress biomarkers, and protein kinases. In clinical trials, curcumin as an adjuvant has significantly boost-up the efficacy of many proven drugs in the management of arthritis, neurodegenerative disorder, oral infection, and gastrointestinal disorders. Moreover, clinical studies have suggested curcumin as an appropriate candidate for the prevention and/or management of various cancers via regulation of signaling molecules including NF-kB, cytokines, C-reactive protein, prostaglandin E2, Nrf2, HO-1, ALT, AST, kinases, and blood profiles. This article highlights plethora of clinical trials that have been conducted on curcumin and its derivatives in the management of several ailments. Besides, it provides recent updates to the investigators for conducting future research to fulfill the current gaps to expedite the curcumin utility in clinical subjects bearing different pathological states.

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin-induced allergic-asthma model in guinea-pigs: Evidences from ex vivo, in silico and in vivo studies.

BACKGROUND: Tylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma. However, only few scientific studies have been performed in the past to validate its antiasthmatic potential. OBJECTIVES: The present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T. indica. METHODS: The most active fraction of T. indica leaves selected through bio-guided activity was subjected to liquid chromatography-mass spectrometry (LC-MS) analysis for chemical profiling. The binding affinity of identified compounds in fraction towards M3 and H1 receptors was determined by molecular docking study. F-2 (chloroform fraction prepared from methanolic extract of T. indica leaves) was examined for its smooth muscle relaxant properties using isolated trachea of guinea-pig. Further, F-2 was evaluated through in vivo studies employing ovalbumin-induced asthma model in guinea-pigs. RESULTS: F-2 was found most effective in bioassay-guided fractionation. Characterization by LC-MS analysis revealed presence of five major bioactive compounds in F-2 that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that F-2 could significantly relax tracheal rings via targeting multiple signalling pathways videlicet, namely, noncompetitive antagonism of the histamine and muscarinic receptors, ß2-adrenergic stimulation and activation of soluble guanylyl cyclase. In in vivo studies, F-2 ameliorated airway hyperresponsiveness and decreased broncho alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE). CONCLUSION: These results confirm the traditional use of T. indica as an antiasthmatic agent which are evidenced through ex vivo, in silico and in vivo studies.

Cedrus deodara (Roxb. ex D.Don) G.Don bark fraction ameliorates metabolic, endocrine and ovarian dynamics in rats experiencing polycystic ovarian syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Ayurvedic system of medicine, Cedrus deodara bark has been utilized as a folk medicine to remove ovarian cysts and treat infertility in females. AIM: The present study is the first to investigate ameliorating potential of C. deodara bark on testosterone propionate and high-fat diet-induced polycystic ovarian syndrome in experimental rats. MATERIALS AND METHODS: LC-MS analysis of the fraction selected through bioassay-guided approach employing uterine relaxant activity was performed to determine the bioactive constituents present in it. Further, the identified compounds were docked on the catalytic site of the androgen receptor and insulin receptor substrate-1. Later, the fraction was investigated against testosterone propionate and high-fat diet-induced PCOS in rats. RESULTS: Chloroform fraction (F1) of the plant bark was found most active in uterine smooth muscle relaxant activity. LC-MS analysis of F1 indicated the presence of key flavonoids namely deodarin, cedrin, deodardione, and cedrusinin. Afterward, a molecular docking study of these compounds revealed impressive binding interactions with androgen receptor and insulin receptor substrate-1. Besides, in vivo studies, treatment with F1 significantly restored the estrous cycle in rats from the diestrus phase in a dose-dependent manner. Also, the disturbed metabolic and endocrine profile was markedly improved in rats. Later, histopathological analysis revealed the presence of a large number of mature follicles and corpora lutea in F1-treated rats. CONCLUSION: In a nutshell, F1 exhibited promising beneficial effects in PCOS and associated conditions via amelioration of metabolic, endocrine, and ovarian dynamics in experimental rats.

Quality-by-design-based engineered liposomal nanomedicines to treat cancer: an in-depth analysis.

Engineered nano-sized liposomes have attained the highest success rate in commercialization among the reported nanomedicines. However, developing industrially acceptable nanoliposomes is still challenging because the process, formulation factors and even their properties may critically influence the desired attributes of the final nanoliposomal product. Implementation of quality-by-design (QbD) in nanoliposomal fabrication has led to revolutionary advancement int better analysis of the interacting factors (drug and lipid ratio, hydration, sonication, etc), which, in turn, leads to better product performance with predefined attributes (entrapment efficiency percentage, drug release time and pattern, vesicles size, polydispersity index, surface charge and surface morphology). This review provides a summary of decade of research and an in-depth analysis of QbD-based nanoliposomes developed to address different cancers. The review aims to provide complete details of QbD-inspired nanoliposomal development from process to application.

This review describes liposomal nanomedicines manufactured via applying quality-by-design (QbD) principals/methods for the treatment of cancer. QbD is industrially applicable technique of manufacturing for emerging pharmaceutical nano-formulations owing to its benefits, including reduced cost, a smaller number of trials, high risk assessment and control over different formulation factors.

Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways.

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.

The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer's disease.

Fatty acid amide hydrolase (FAAH) is a prominent enzyme of the endocannabinoid system that degrades endogenous cannabinoid anandamide and oleamide. These lipid amides are involved in reducing neuroinflammation, pain and regulation of other neurological-related activities including feeding behaviours, sleep patterns, body temperature, memory processes and locomotory activity. Many of these activities are affected in most neurological disorders. Increased levels of brain FAAH expressions are speculated to correlate with decreased levels of lipid amides and increased AD-related symptoms. Thus, inhibition of FAAH shows promising potential in amelioration of symptoms associated with Alzheimer's disease (AD). The review aims at establishing the detrimental role of increased FAAH expression in AD and highlights the translational potential and therapeutic application of FAAH inhibitors in AD.

Cedrus deodara (Roxb. ex D.Don) G.Don: A review of traditional use, phytochemical composition and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus deodara (Roxb. ex D.Don) G.Don (Family: Pinaceae) is a medicinal tree traditionally important and well mentioned in traditional system of medicine of India, Pakistan, China, Korea etc. for its use in the management of skin diseases, microbial infections, joint disorders, asthma, kidney stones, ulcer, brain disorders and immunological disorders. AIM AND OBJECTIVES: This review provides an insight into the information available regarding traditional uses, ethnobotany, phytochemistry and, pharmacological profiling of C. deodara crude extract, its isolated compounds and, fractions, to explore its potential for the development of novel therapeutic agents. MATERIAL AND METHODS: Various databases including Scopus, Google Scholar, Science Direct, ACS, Wiley, Web of Science, Springer Link and, PubMed were used to collect all the appropriate information available in previously published literature related to this plant. Besides, other official electronic sources viz. Encyclopedia Britannica and Northern Regional Center, Botanical Survey of India, theplantlist.org. and relevant book chapters and books were also explored. RESULTS: C. deodara is a popular medicinally active tree, traditionally used in the form of decoction, syrup, oil, powder, and extract alone or in combination with other herbs for the management of different ailments viz. asthma, ulcers, bone fractures, sprains rheumatism, boils, leprosy, etc. Phytochemical studies reported 105 chemical constituents from different parts of the plant, most of them belong to a class of terpenoids and flavonoids. Crude extracts, essential oils, fractions, and isolated compounds of C. deodara exhibited some important pharmacological activities including anticancer, antimicrobial, antifungal, analgesic, anti-inflammatory, neuroprotective, antidiabetic, antiurolithiatic, antiarthritic and, antiasthmatic. CONCLUSION: Present article delivers in-depth information on botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology. C. deodara has been in practice among indigenous people of India, Pakistan, Nepal, Korea, China, Nigeria and Russia and 28 different ethnicities for the management of approximately 40 diseases. Bioactive compounds particularly cedrin, himachalol, himachalene and atlantone are recognized as key constituents for observed pharmacological activities of C. deodara. However, further in-depth studies involving bio-guided fractionation, isolation, identification using advanced techniques to afford some new therapeutically active phytoconstituents in the management of different diseases. Preliminary pharmacological investigations on different extracts and fractions of C. deodara partially validated its traditional claims in different ailments such as skin diseases, asthma, neurological disorders, arthritis, microbial infections, gastric disturbances, and inflammation. However, immediate attempts are required to establish its mechanism of action, efficacy, dosage range, and safety in combating different pathological states.

Curcumin: An Insight into Molecular Pathways Involved in Anticancer Activity.

Curcuma longa has been mentioned in the Indian system of medicine for the management of a wide range of diseases. C. longa and its metabolites like curcumin, ar-turmerone, methylcurcumin, demethoxy-curcumin, and bisdemethoxycurcumin have also been reported to be beneficial in various types of cancer. Curcumin elicits anticancer properties chiefly by triggering apoptotic pathways in cancer cells. The properties are facilitated through diverse signaling pathways viz. pathways mediated by NF-kB, WNT/ß-catenin pathway COX-2, LOX, STAT3, prostaglandin E2, phosphorylase kinase, VEGF, AKT, AP1, STAT3, PI3K, Akt, mTOR, ERK5, AP-1, TGF-b, PPARc, EBPa, NLRP3 inflammasome, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4, etc. The present article highlights curcumin biosynthesis, phytochemistry and diverse molecular pathways involved in regulating several types of secondary messengers to exhibit anticancer activity in almost all the forms of cancer.

Neuroprotective Role of Oral Vitamin D Supplementation on Consciousness and Inflammatory Biomarkers in Determining Severity Outcome in Acute Traumatic Brain Injury Patients: A Double-Blind Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Early management of traumatic brain injury (TBI) is essential. We aimed to evaluate the efficacy of vitamin D over early clinical outcome and serum cytokine levels in patients with moderate to severe brain injury. METHODS: Thirty-five patients with moderate to severe traumatic brain injury who were admitted to the ICU unit were recruited into the study. Subjects were randomly allocated to a treatment regimen comprising either a one-time oral dose of 120,000 IU (two tablets of 60,000 IU each) of vitamin D (n = 20) or 8 mg of saccharide (two tablets of 4 g each) as placebo (n = 15). The main parameters evaluated included duration of mechanical ventilation and ICU stay, Glasgow Coma Scale (GCS) and cytokine levels (interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, IL-2). RESULTS: The results indicated an improvement in the level of consciousness after 7 days in the vitamin D-treated group compared with placebo. An elevation in GCS score by 3.86 units in the vitamin D-treated group with a 0.19-unit descent in the control group was recorded. Duration of mechanical ventilation was reduced in the vitamin D-treated group compared with the control group (4.7 days vs. 8.2 days, p value 0.0001). A noticeable reduction was recorded in inflammatory biomarkers (cytokines) in the vitamin D-treated group (IL-6 p = 0.08, TNF-α p = 0.02, IL-2 p = 0.36) with notable elevation in IFN-γ (p = 0.65) compared to the control group. CONCLUSION: In the acute phase of moderate to severe traumatic brain injury, vitamin D supplementation plays a vital role and has a favourable effect on the consciousness level of patients. Clinical trial Registry (CTRI) No. CTRI/2019/05/019259.