Targeting the vivid facets of apolipoproteins as a cardiovascular risk factor in rheumatoid arthritis.

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.

Reactive oxygen species (ROS)-mediated oxidative stress in chronic liver diseases and its mitigation by medicinal plants.

Reactive oxygen species (ROS) play a crucial role in cell survival regulation, and its low levels may act as indicators to encourage cellular proliferation. In contrast, elevated levels of ROS may lead to apoptosis. Stability between generating and eliminating ROS allows the retention of effective functioning of redox-sensitive signaling proteins under physiologic conditions. Cells typically maintain redox homeostasis to guarantee appropriate responses to internal and external stimuli. However, oxidative stress occurs when the oxidation product level exceeds the number of standard antioxidant systems. ROS can cause harm to all types of hepatic cells, including endothelial cells, hepatocytes, Kupffer cells, and stellate cells. High levels of ROS may lead to tissue edema, ischemia, fibrosis, cell death, or malignant transformation and may eventually lead to complete tissue damage. Antioxidants in our body exist in a homeostatic balance with other enzymes involved in the repair of cellular functions in addition to the non-enzymatic molecules such as urate, bilirubin, several vitamins, and reduced glutathione to maintain the levels of ROS in the interest of cellular homeostasis. This balance may, however, get disturbed in case of acute or chronic liver injury due to the accumulation of ROS. In the current manuscript, we aim to review the relevance of oxidative stress and its indicator of liver injury in chronic liver diseases such as alcoholic and non-alcoholic fatty liver diseases and hepatitis. Since reactive oxidation species may also lead to lipid peroxidation and promote ferroptosis, we have also evaluated their impact on epigenetic modifications, such as oxidative damage to histone proteins and DNA methylation, and the differential expression of genes related to cellular injury. We also want to highlight the potential of traditional herbal medicines as redox regulators for managing chronic liver diseases.

Understanding the promising role of antibody drug conjugates in breast and ovarian cancer.

A nascent category of anticancer therapeutic drugs called antibody-drug conjugates (ADCs) relate selectivity of aimed therapy using chemotherapeutic medicines with high cytotoxic power. Progressive linker technology led to the advancement of more efficacious and safer treatments. It offers neoteric as well as encouraging therapeutic strategies for treating cancer. ADCs selectively administer a medication by targeting antigens which are abundantly articulated on the membrane surface of tumor cells. Tumor-specific antigens are differently expressed in breast and ovarian cancers and can be utilized to direct ADCs. Compared to conventional chemotherapeutic drugs, this approach enables optimal tumor targeting while minimizing systemic damage. A cleavable linker improves the ADCs because it allows the toxic payload to be distributed to nearby cells that do not express the target protein, operating on assorted tumors with dissimilar cell aggregation. Presently fifteen ADCs are being studied in breast and ovarian carcinoma preclinically, and assortment of few have already undergone promising early-phase clinical trial testing. Furthermore, Phase I and II studies are investigating a wide variety of ADCs, and preliminary findings are encouraging. An expanding sum of ADCs will probably become feasible therapeutic choices as solo agents or in conjunction with chemotherapeutic agents. This review accentuates the most recent preclinical findings, pharmacodynamics, and upcoming applications of ADCs in breast and ovarian carcinoma.

Chrysin restores the cardioprotective effect of ischemic preconditioning in diabetes-challenged rat heart.

Background: Ischemic preconditioning (IPC) is the utmost capable design to achieve protection over ischemia-reperfusion injury (I/R), but this phenomenon gets attenuated during various pathological conditions like diabetes. Chrysin exhibits cardioprotection in various experiments however, its therapeutic potential on IPC-mediated cardioprotection via PI3K-Akt-eNOS pathway in streptozotocin (STZ) triggered diabetes-challenged rat heart is yet to be assessed. For that reason, the experiment has been planned to investigate chrysin's effect on the cardioprotective action of IPC involving the PI3K-Akt-eNOS cascade in rat hearts challenged to diabetes. Methods: The project was accomplished through means of absorbance studies for biochemical parameters, infarct size measurement (TTC stain) and coronary flow. Results: The findings of the present study revealed that STZ drastically augmented the serum glucose level and the chrysin significantly reversed the IPC-stimulated increased coronary flow, nitrite release, and reduced LDH (lactate dehydrogenase), CK-MB (creatine kinase) activities as well as infarct size in diabetes-induced rat heart. Furthermore, chrysin also reversed the IPC-induced reduction in oxidative stress in an isolated Langendorff's perfused diabetic rat heart. Moreover, four episodes of preconditioning by either PI3K or eNOS inhibitor in chrysin-pretreated diabetic rat hearts significantly abolished the protective effect of chrysin. Conclusion: Consequently, these observations suggested that chrysin increases the therapeutic efficiency of IPC in mitigating I/R injury via PI3K-Akt-eNOS signalling in diabetes-challenged rat hearts. Hence, chrysin could be a potential alternative option to IPC in diabetic rat hearts.

Understanding the mechanistic pathways and clinical aspects associated with protein and gene based biomarkers in breast cancer.

Cancer is one of the most widespread and severe diseases with a huge mortality rate. In recent years, the second-leading mortality rate of any cancer globally has been breast cancer, which is one of the most common and deadly cancers found in women. Detecting breast cancer in its initial stages simplifies treatment, decreases death risk, and recovers survival rates for patients. The death rate for breast cancer has risen to 0.024 % in some regions. Sensitive and accurate technologies are required for the preclinical detection of BC at an initial stage. Biomarkers play a very crucial role in the early identification as well as diagnosis of women with breast cancer. Currently, a wide variety of cancer biomarkers have been discovered for the diagnosis of cancer. For the identification of these biomarkers from serum or other body fluids at physiological amounts, many detection methods have been developed. In the case of breast cancer, biomarkers are especially helpful in discovering those who are more likely to develop the disease, determining prognosis at the time of initial diagnosis and choosing the best systemic therapy. In this study we have compiled various clinical aspects and signaling pathways associated with protein-based biomarkers and gene-based biomarkers.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

Current trends in epigenetic, cellular and molecular pathways in management of rheumatoid arthritis.

Rheumatoid arthritis is a systemic chronic polyarticular autoimmune disorder of joints and joint membrane mainly affecting feet and hands. The pathological manifestation of the disease includes infiltration of immune cells, hyperplasia of the lining of synovium, formation of pannus and bone and cartilage destruction. If left untreated, the appearance of small focal necrosis, adhesion of granulation, and formation of fibrous tissue on the surface of articular cartilage is noted. The disease primarily affects nearly 1% of the population globally, women being more affected than men with a ratio 2:1 and can initiate regardless of any age. The synovial fibroblast in rheumatoid arthritis individuals exhibits an aggressive phenotype which upregulates the manifestation of protooncogenes, adhesive compounds, inflammatory cytokines and matrix-deteriorating enzymes. Apart from the inflammatory effects of cytokines, chemokines are also noted to induce swelling and pain in arthritic individuals by residing in synovial membrane and forming pannus. The current treatment of rheumatoid arthritis includes treatment with non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, treatment with biologics such as inhibitors of TNF-α, interleukins, platelet activating factor, etc. which provides significant relief from symptoms and aids in management of the disease. The current review highlights the pathogenesis involved in the onset of rheumatoid arthritis and also covers epigenetic, cellular and molecular parameters associated with it to aid better and advanced therapeutic approaches for management of the debilitating disease.

Design and synthesis of neoteric benzylidene amino-benzimidazole scaffolds for antioxidant and anti-inflammatory activity.

Aim: To design a series of neoteric benzylidene amino-benzimidazole derivatives and to synthesize and evaluate them for anti-inflammatory and antioxidant potential. Methods: The designed target scaffolds were synthesized and appraised for in vitro antioxidant action and in vivo anti-inflammatory potential. AutoDock Vina software was employed for design; the Mannich reaction was used for synthesis; and antioxidant and anti-inflammatory potential were demonstrated by the 2,2-diphenyl-1-picryl hydrazyl free-radical scavenging assay and carrageenan-induced paw edema method, respectively. Results: Methyl-incorporating molecules 3-(2-((2-methylbenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one (6c) and 3-(2-((4-methylbenzylidene)amino-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one (6j) showed remarkable antioxidant and anti-inflammatory action, followed by compounds 6f, 6e and 6i containing 3-CH3, 2-OH, 4-F substituents, respectively. Conclusion: The designed analogs were dynamically confined within the active site of cyclooxygenase-2, and in vitro and in vivo results agreed with molecular docking studies.

Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

Unveiling the Pharmacological and Nanotechnological Facets of Daidzein: Present State-of-the-Art and Future Perspectives.

Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4',7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.

Molecular Aspects and Therapeutic Implications of Herbal Compounds Targeting Different Types of Cancer.

Due to genetic changes in DNA (deoxyribonucleic acid) sequences, cancer continues to be the second most prevalent cause of death. The traditional target-directed approach, which is confronted with the importance of target function in healthy cells, is one of the most significant challenges in anticancer research. Another problem with cancer cells is that they experience various mutations, changes in gene duplication, and chromosomal abnormalities, all of which have a direct influence on the potency of anticancer drugs at different developmental stages. All of these factors combine to make cancer medication development difficult, with low clinical licensure success rates when compared to other therapy categories. The current review focuses on the pathophysiology and molecular aspects of common cancer types. Currently, the available chemotherapeutic drugs, also known as combination chemotherapy, are associated with numerous adverse effects, resulting in the search for herbal-based alternatives that attenuate resistance due to cancer therapy and exert chemo-protective actions. To provide new insights, this review updated the list of key compounds that may enhance the efficacy of cancer treatment.

The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson's disease animal model.

Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.

Postulating the possible cellular signalling mechanisms of antibody drug conjugates in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world. Although the basic pathology of the disease is elucidated, it is difficult to restore or prevent the worsening of neurodegeneration and its symptoms. Antibody and small molecule-based approaches have been studied and are in study individually, but a combined approach like conjugation has not been performed to date. The conjugation between antibodies and drugs which are already used for Alzheimer's treatment or developed specifically for this purpose may have better efficacy and dual action in mitigating Alzheimer's disease. A probable mechanism for antibody-drug conjugates in Alzheimer's disease is discussed in the present review.

Obtaining an Oily Ingredient Rich in PUFAS and Tocopherols and a High-Nutritional-Value Flour from Beans (Phaseolus vulgaris L.) by Supercritical CO2 Extraction.

The objective of this work was to carry out a preliminary study of the fractionation by supercritical CO2 (sc-CO2) extraction of two varieties of Peruvian beans (Phaseolus vulgaris L.), white (WB) and red (RB), to obtain two novel products: an oil rich in essential fatty acids and tocopherols and a defatted flour with high nutritional value and amino acids. The extraction temperature and pressure were optimized using the response surface methodology (RSM) and the extraction kinetics were optimized using the Spline equation. The results revealed that the best extraction conditions for WB and RB were 396.36 Bar, 40.46 °C, with an efficiency of 1.65%; and 391.995 Bar, 44.00 °C, with an efficiency of 1.12%, respectively. The WB and RB oils presented a high degree of polyunsaturation (63.2 and 52.8%, respectively), with oleic, linoleic, and linolenic fatty acids prevailing. Gamma-tocopherol was the predominant antioxidant in both oils. The residual flours (WB and RB) obtained after extraction with sc-CO2 had a high average content of proteins (23%), carbohydrates (61%), and minerals (3%). The limiting amino acids of WB were: Fen + Tyr, Leu, Lys, and in RB, only Leu was limiting. The viscosity of the solutions (20%) of the WB and RB flours mainly adjusted to the Waele's Ostwald model (r = 0.988). It is concluded that both products (oil and bean flour) obtained in an optimized manner using an eco-friendly technology with sc-CO2 have high nutrient and bioactive component content and can be used in the development of new ingredients and healthy foods of plant origin.

Appraisal of the pharmacokinetic profile, histopathology and stability studies of a fast dissolving oral film based on natural polysaccharide.

The present research is designed to evaluate the pharmacokinetic profile, histological evaluation, and stability studies of an orodispersible film (ODF) of tizanidine (TZ) and meloxicam (MX) prepared from a natural polysaccharide, i.e., xanthan gum. In vivo release study of TZ and MX was performed in rabbits and results indicated the better pharmacokinetics parameters and improved the oral bioavailability when compared to the oral aqueous suspension and solution of TZ and MX, respectively. The intermediate stability studies were performed at 30±2°C and 65±5% RH, whereas, the accelerated stability studies were carried out at 40±2°C and 75±5% RH, respectively for the duration of six months and results indicated that the ODF was stable for six months without any substantial difference in essential physico-chemical parameters, mechanical attributes, and morphological constraints. The toxicity profile of ODF was determined through histopathology of vital organs after administering the ODF to the rabbits. Histopathology revealed that the tissues of all vital organs are normal and did not exhibit any abnormalities, lesions, or hemorrhage. Therefore, the ODF prepared from xanthan gum exhibited a non-toxic and stable formulation with a better pharmacokinetics profile of MX and TZ.

Emergence of nutriments as a nascent complementary therapy against antimicrobial resistance.

With these growing and evolving years, antimicrobial resistance has become a great subject of interest. The idea of using natural productive ways can be an effective measure against antimicrobial resistance. The growing prevalence of antimicrobial resistance indicates that advanced natural approaches are a topic of concern for fighting the resistance. Many natural products including essential oils, flavonoids, alkaloids and botanicals have been demonstrated as effective bactericidal agents. In this review, we will discuss in detail about the relevance of such natural products to tackle the problem of antimicrobial resistance, antibiotic adjuvants that aim towards non-essential bacterial targets to reduce the prevalence of resistant bacterial infections, latest bioinformatics approach towards antibacterial drug discovery along with an understanding of biogenic nanoparticles in antimicrobial activity.

Fermentation of Vaccinium floribundum Berries with Lactiplantibacillus plantarum Reduces Oxidative Stress in Endothelial Cells and Modulates Macrophages Function.

Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as Lactiplantibacillus plantarum, enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with Lactiplantibacillus plantarum on the antioxidant and immunomodulatory effects of Pushgay berries (Vaccinium floribundum, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.7. Polyphenol content was assayed by Folin-Ciocalteu and HPLC-MS/MS analysis. The effects of berries solutions on cell viability or proliferation were assessed by WST8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and Lactate dehydrogenase (LDH) release, Trypan blue exclusion test, and Alamar blue assay. Antioxidant activity was evaluated by a cell-based chemiluminescent probe for the detection of intracellular H2O2 production in HUVECs. Heme oxygenase-1 (HO-1) expression levels were investigated by RT-qPCR. Glutathione reductase (GR), glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) activities, as markers of intracellular antioxidant defense, were evaluated by spectrophotometric analysis. The immunomodulatory activity was examined in RAW 264.7 by quantification of inducible nitric oxide synthase (iNOS) and Tumor Necrosis Factor-alpha (TNFα) by RT-qPCR. Data showed that fermentation of Pushgay berries (i) enhances the content of quercetin aglycone, and (ii) increases their intracellular antioxidant activity, as indicated by the reduction in H2O2-induced cell death and the decrease in H2O2-induced HO-1 gene expression in HUVECs treated for 24 h with fermented berries solution (10 µg/mL). Moreover, treatment with Pushgay berries for 72 h (10 µg/mL) promotes cells growth in RAW 264.7, and only fermented Pushgay berries increase the expression of iNOS in the same cell line. Taken together, our results show that LAB fermentation of Pushgay berries enhances their antioxidant and immunomodulatory properties.

Detailed investigation of the composition and transformations of phenolic compounds in fresh and fermented Vaccinium floribundum berry extracts by high-resolution mass spectrometry and bioinformatics.

INTRODUCTION: Blueberries are known for their very high content of biologically active phenolic compounds; nonetheless, differently from the North American and European species of blueberries, Neotropical blueberries have not been extensively studied yet. OBJECTIVES: In the present paper, the phenolic composition of Vaccinium floribundum Kunth, which is endemic to the Andean regions and grows 1,600 to 4,500 meters above sea level, was investigated by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). Native and fermented berries were compared in terms of phenolic composition as well as antioxidant activity, total phenolic content, and total anthocyanin content. MATERIALS AND METHODS: V. floribundum native and fermented berries were extracted and analyzed by UHPLC-HRMS. The acquired datasets were processed by Compound Discoverer 3.1 using a dedicated data analysis workflow that was specifically set up for phenolic compound identification. RESULTS: In total, 309 compounds were tentatively identified, including anthocyanins, flavonoids, phenolic acids, and proanthocyanidins. The molecular transformations of phenolic compounds during fermentation were comprehensively investigated for the first time, and by a customized data processing workflow, 13 quinones and quinone methides were tentatively identified in the fermented samples. Compared to other species of the genus Vaccinium, a peculiar phenolic profile is observed, with low abundance of highly methylated compounds. CONCLUSION: Andean berries are a rich source of a wide variety of phenolic compounds. Untargeted MS analyses coupled to a dedicated data processing workflow allowed expanding the current knowledge on these berries, improving our understanding of the fate of phenolic compounds after fermentation.

Anti-migraine activity of freeze-dried latex obtained from Calotropis gigantea Linn.

Migraine which is characterized by a pulsating headache affected an estimated population of 12% worldwide. Herbal products like latex derived from Calotropis gigantea R. Br. (Asclepiadaceae) are a representative intervention to treat migraine traditionally. However, post-harvesting stability issues of latex affect its biological potential. Freeze-drying has been successfully employed for the encapsulation of herbal bioactive compounds resulting in stable dried preparations. Latex derived from Calotropis gigantea (C. gigantea) was microencapsulated using chitosan by freeze-drying (FDCG) method and compared with sun ray-dried latex (ADCG). Current investigation was aimed to improve the shelf life of latex by freeze-drying microencapsulation technique and evaluation of its anti-migraine potential. Dried latex powders (ADCG and FDCG) were evaluated in terms of phenolic content, coloring strength, first-order kinetic, color parameters (L*, a*, b*, C*, and E*), moisture, water activity, solubility, and hygroscopicity. Additionally, apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity were used to evaluate the anti-migraine potential of powdered latex. FDCG showed good physicochemical properties due to its higher concentration of phenolic and flavonoid contents. Moreover, FDCG significantly reduced the apomorphine-induced climbing behavior, L-5-HTP-induced syndrome, and MK-801-induced hyperactivity in a dose-dependent manner through an interaction of dopaminergic and serotonergic receptors. In conclusion, the method developed for shelf life improvement of latex offered maximum protection over a period of 10 weeks with retaining its natural biological potential; thus, it can be effectively utilized in the treatment or management of migraine. Anti-migraine effect of Calotropis gigantea freeze-dried latex by inhibition of dopamine and serotonin receptors (D1 and D2: dopamine receptors; 5-HT: serotonin receptors); yellow color represents serotonergic, and blue color indicates dopaminergic neurons.