Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro.

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1ß and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.

Exploring the potentials of Ziziphus mauritiana Lam. seed kernel oil as pharmaceutical oil base: Physicochemical characterization and ketoconazole soap formulation.

Ziziphus mauritiana Lam. (Rhamnaceae) is a large spiny shrub or small tree, native to the Indian subcontinent that can reach a maximum height of 9-15 m. This plant stands as a renowned tropical fruit variety, commonly recognized as the Indian plum, Desert apple, or Indian Jujube. The objective of this study was to examine the standard physicochemical parameters of Z. mauritiana seed kernel oil and to formulate the ketoconazole soap (2 % w/w), using the obtained oil, as a base. The oil was obtained through hexane extraction from the seed kernels. To formulate pharmaceutical ketoconazole soap, Z. mauritiana seed kernel oil was subjected to a basic saponification reaction using potassium hydroxide. All the examined physicochemical parameters, namely acid value (4.71 mg KOH/g), saponification value (229.18 mg KOH/g), peroxide value (4.15 milliequivalents KOH/g), ester value (224.47 mg KOH/g), iodine value (11.19 mg KOH/g), refractive index (1.448), pH (5.93), viscosity (89 cP), and specific gravity (0.912 g/mL) were within the acceptable range for industrial purposes. The examination of quality control parameters, namely drug content (99.49 %), total fatty matter (71.13 %), foam retention time (17.21 min), foam height (18.56 cm), moisture content (9.14 %), and pH (7.16) indicated that the newly formulated ketoconazole soap complied with the acceptable limits. In summary, our research demonstrated the excellent physicochemical stability of Z. mauritiana seed kernel oil and its suitability as a soap base, supporting its promising prospects for cost-effective production of cosmetics, soaps, and shampoos in the pharmaceutical and cosmeceutical industries, reducing reliance on synthetic bases.

Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.

Existing therapeutic interventions for controlling cancer are limited and associated with side effects. Furthermore, the recurrence of cancer poses a significant challenge to the cure of cancer. Therefore, avenues are wanted to find novel therapies for cancer treatment and cancer recurrence. In this review, we have highlighted that lactoferrin (LF) and activated protein C (APC) carry enormous potential in cancer treatment. Studies have shown that the decreased level of APC and impaired function of APC are associated with cancer progression and cancer-related mortality. Moreover, APC plays an important role in preventing prothrombotic state-mediated cancer progression and deaths. LF can also inhibit the progression of cancer by controlling the generation of reactive oxygen species, triggering the apoptosis of cancer cells, arresting the cell cycle and hindering the angiogenesis process. Additionally, APC and LF could have the potential to inhibit neutrophil extracellular traps (NETs) formations which are involved in cancer progression and the reawakening of dormant cancer cells. Hence, in this review, the anticancer potential and mechanism of APC and LF along with their potential to mitigate inflammation and NETs-mediated cancer progression and recurrence has been discussed. Additionally, possible future strategies to develop effective and safe anticancer treatment using LF and APC have also been discussed in this review.

Yellow Himalayan Raspberry (Rubus ellipticus Sm.): Ethnomedicinal, Nutraceutical, and Pharmacological Aspects.

Yellow Himalayan raspberry (Rubus ellipticus Sm., Rosaceae) is a native species of the Indian subcontinent, Southern China, and the Philippines, which has been historically used as a traditional medicine and food. All of the parts of this plant have been used in traditional medicine to treat respiratory ailments, diabetes, and gastrointestinal disorder, and as an anti-infective agent. The scientific evaluation revealed a richness of macronutrients, micronutrients, and minerals in the fruits, indicating its potential use as a nutraceutical. Furthermore, this plant has been found to be rich in various secondary metabolites, including polyphenols, flavonoids, anthocyanins, tannins, and terpenoids. Ascorbic acid, kaempferol, gallic acid, and catechin are some of the compounds found in this plant, which have been widely discussed for their health benefits. Furthermore, various extracts and compounds obtained from R. ellipticus have shown antioxidant, antidiabetic, anticancer, anti-inflammatory, nephroprotective, antipyretic, anticonvulsant, and anti-infective activities investigated through different study models. These findings in the literature have validated some of the widespread uses of the fruits in folk medicinal systems and the consumption of this nutritious wild fruit by local communities. In conclusion, R. ellipticus holds strong potential for its development as a nutraceutical. It can also improve the nutritional status of villagers and uplift the economy if properly utilized and marketed.

Major phenolic compounds, antioxidant, antimicrobial, and cytotoxic activities of Selinum carvifolia (L.) collected from different altitudes in India.

Antibiotic resistance poses a serious threat to public health, raising the number of diseases in the community. Recent research has shown that plant-derived phenolic compounds have strong antimicrobial, antifungal, and cytotoxic properties against a variety of microorganisms and work as great antioxidants in such treatments. The goal of the current work is to evaluate the anticancerous, antibacterial, antifungal, antioxidant, and cytotoxicity activities in the extracts of the different plant parts (leaves, stems, and roots) of S. carvifolia (L.) L. This is a medicinally important plant and has been used for different kinds of diseases and ailments such as hysteria and seizures. The phenolic compounds from the different plant parts were analyzed using HPLC and the following were found to be present: chlorogenic acid, gallic acid, rutin, syringic acid, vanillic acid, cinnamic acid, caffeic acid, and protocatechuic acid. Gallic acid was found to have the highest concentration (13.93 mg/g), while chlorogenic acid (0.25 mg/g) had the lowest. The maximum TPC value, which ranged from 33.79 to 57.95 mg GAE/g dry extract weight, was found in the stem. Root extract with 9.4 mg RE/g had the greatest TFC level. In the leaf and stem extracts, the RSC ranged from 0.747 mg/mL to 0.734 mg/1 mL GE/g dry extract weight, respectively. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to measure in vitro antioxidant activity. In a concentration-dependent way, promising antioxidant activity was reported. Moreover, 3,5-dinitrosalicylic acid (DNSA) and the Folin-Ciocalteu phenol reagent technique were used to determine reducing sugar content and total phenolic content, respectively. Antibacterial activity against eight strains (MIC: 250-1,000 µg/mL) was analyzed, and the stem extract exhibited maximum activity. Antifungal activity was also assessed, and potent activity was reported especially in the extract obtained from the stem. Cytotoxicity was evaluated using an MTT assay in the A549 cell line, where different doses (0.0625, 0.125, 0.25, 0.5, and 1 mg/mL) of leaf, root, and stem extracts were used. Treatment with these extracts reduced the cell viability, indicating that S. carvifolia may possess anticancer potential, which can be of great therapeutic value.

Amamine, an isoquinoline alkaloid from the Kitasatospora sp. HGTA304.

Amamine (1), a new isoquinoline alkaloid, was isolated from the culture extract of an actinomycete Kitasatospora sp. HGTA304. The structure of 1 was determined by NMR and MS analyses in combination with UV data. Compound 1 displayed α-glucosidase inhibitory potential (IC50 value of 56 µM) compared with acarbose (IC50 value of 549 µM) as standard.

Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer.

Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds' anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid-lipid and liquid-lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies.

Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials.

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.

Harnessing polyphenol power by targeting eNOS for vascular diseases.

Vascular diseases arise due to vascular endothelium dysfunction in response to several pro-inflammatory stimuli and invading pathogens. Thickening of the vessel wall, formation of atherosclerotic plaques consisting of proliferating smooth muscle cells, macrophages and lymphocytes are the major consequences of impaired endothelium resulting in atherosclerosis, hypercholesterolemia, hypertension, type 2 diabetes mellitus, chronic renal failure and many others. Decreased nitric oxide (NO) bioavailability was found to be associated with anomalous endothelial function because of either its reduced production level by endothelial NO synthase (eNOS) which synthesize this potent endogenous vasodilator from L-arginine or its enhanced breakdown due to severe oxidative stress and eNOS uncoupling. Polyphenols are a group of bioactive compounds having more than 7000 chemical entities present in different cereals, fruits and vegetables. These natural compounds possess many OH groups which are largely responsible for their strong antioxidative, anti-inflammatory antithrombotic and anti-hypersensitive properties. Several flavonoid-derived polyphenols like flavones, isoflavones, flavanones, flavonols and anthocyanidins and non-flavonoid polyphenols like tannins, curcumins and resveratrol have attracted scientific interest for their beneficial effects in preventing endothelial dysfunction. This article will focus on in vitro as well as in vivo and clinical studies evidences of the polyphenols with eNOS modulating activity against vascular disease condition while their molecular mechanism will also be discussed.

Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues.

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca2+ -dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca2+ -dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety.

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

The potential of pumpkin seed oil as a functional food-A comprehensive review of chemical composition, health benefits, and safety.

The growing interest in foods that can be beneficial to human health is bringing into focus some products that have been used locally for centuries but have recently gained worldwide attention. One of these foods is pumpkin seed oil, which has been used in culinary and traditional medicine, but recent data also show its use in the pharmaceutical and cosmetic industries. In addition, some sources refer to it as a potential functional food, mainly because it is obtained from pumpkin seeds, which contain many functional components. However, the production process of the oil may affect the content of these components and consequently the biological activity of the oil. In this review, we have focused on summarizing scientific data that explore the potential of pumpkin seed oil as a functional food ingredient. We provide a comprehensive overview of pumpkin seed oil chemical composition, phytochemical content, biological activity, and safety, as well as the overview of production processes and contemporary use. The main phytochemicals in pumpkin seed oil with health-related properties are polyphenols, phytoestrogens, and fatty acids, but carotenoids, squalene, tocopherols, and minerals may also contribute to health benefits. Most studies have been conducted in vitro and support the claim that pumpkin seed oil has antioxidant and antimicrobial activities. Clinical studies have shown that pumpkin seed oil may be beneficial in the treatment of cardiovascular problems of menopausal women and ailments associated with imbalance of sex hormones.

Citrus maxima (Brum.) Merr. (Rutaceae): Bioactive Chemical Constituents and Pharmacological Activities.

Citrus maxima (Burm). Merr. (family Rutaceae), commonly known as Pomelo, is an ethnomedicinally, pharmacologically, and phytochemically valued species. Various ethnomedicinal reports have revealed the use of C. maxima for cough, fever, asthma, diarrhea, ulcer, and diabetes and as a sedative. Numerous phytochemicals have been reported from C. maxima such as polyphenols, terpenoids, sterols, carotenoids, vitamins, and amino acids. The plant possesses significant bioactivities like antioxidant, antimicrobial, anti-inflammatory, analgesic, anticancer, antidiabetic, anti-Alzheimer's disease, insecticidal, anxiolytic, hepatoprotective, antimalarial, and antiobesity. Extensive research is necessary to explore the detailed mechanism of action of extracts and compounds to design effective medicines, herbal products, and functional foods.

Bioactive secondary metabolites in Paris polyphylla Sm. and their biological activities: A review.

Paris polyphylla Sm. is an important medicinal plant used to treat a variety of diseases through traditional medicine systems such as Ayurveda, Tibetan traditional medicines, Chinese traditional medicines, and others around the world. The IUCN red list has designated it as "vulnerable" due to a decline in wild population by over-exploitation, habitat degradation, illegal collection for trade and traditional use. This review paper aims to summarize the bioactive secondary metabolites in Paris polyphylla. Paris saponins or steroidal saponins are the main bioactive chemical constituents from this plant that account for more than 80% of the total compounds. For instance, polyphyllin D, diosgenin, paris saponins I, II, VI, VII, and H are steroidal saponins having anticancer activity comparable to synthetic anticancer medicines. Antioxidant, anticancer, anti-leishmaniasis, antibacterial, antifungal, anthelmintic, antityrosinase, and antiviral effects of extracts and pure compounds were also demonstrated in vivo and in vitro. In conclusion, this review summarizes the bioactive components from the P. polyphylla which will be useful to researchers and scientists, and for the development of potential drugs.

Harnessing the therapeutic potential of fisetin and its nanoparticles: Journey so far and road ahead.

Fisetin (FS) is a bioactive flavonoid obtained mostly from apple and strawberry and classified under the category of food supplements due to numerous pharmacological effects against various diseases through multiple mechanistic pathways. It acts as excellent neuroprotective, cardioprotective, anti-invasive, anti-tumorigenic, anti-angiogenic, anticancer, antidiabetics, antioxidant, anti-inflammatory agent. Despite having excellent safety and efficacy profile, FS is very less explored to clinical research either as food supplement or, as therapeutic agent due to its poor aqueous solubility, low bioavailability and reduced blood brain barrier permeability. Multiple mechanistic pathways through which FS elicits its pharmacological actions and the challenges associated with FS that compromises therapeutic efficacy are described in this article. The nanoformulations developed to enhance the bioavailability and therapeutic efficacy of FS are also covered with detailed description of research works carried by various researchers. These include nanoemulsions, liposomes, ethosomes, glycerosomes, polymeric micelles, self-nanoemulsifying drug delivery system and polymeric nanoparticles. Various patents pertaining to extraction/isolation, formula composition and therapeutic uses of FS as well as some clinical studies conducted using FS as active moiety are also enlisted.

Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models.

Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respiratory diseases primarily occur due to prolonged airway inflammation. In addition, critical environmental factors such as cigarette smoke, industrial pollutants, farm dust, and pollens may also exacerbate such diseases. Moreover, alterations in the genetic sequence of an individual, abnormalities in the chromosomes or immunosuppression resulting from bacterial, fungal, and viral infections may also play a key role in the pathogenesis of respiratory diseases. Over the years, multiple in vitro models have been employed as the basis of existing as well as emerging advancements in chronic respiratory disease research. These include cell lines, gene expression techniques, single cell RNA sequencing, cytometry, culture techniques, as well as serum/sputum biomarkers that can be used to elucidate the molecular mechanisms underlying these diseases, and to identify novel diagnostic and management options for these diseases. This review summarizes the current understanding of the pathogenesis of various chronic respiratory diseases derived through in vitro experimental models, where the knowledge obtained from these studies can greatly benefit researchers in the discovery and development of novel screening techniques and advanced therapeutic strategies that could be translated into clinical use in the future.

N-Acetylcysteine Alleviated the Deltamethrin-Induced Oxidative Cascade and Apoptosis in Liver and Kidney Tissues.

Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. N-acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.

Bioactive Chemical Constituents and Pharmacological Activities of Ponciri Fructus.

Ponciri Fructus is a crude drug obtained from the dried immature fruits of Poncirus trifoliata (L). Raf. (Syn. Citrus trifoliata L.). This study aims to compile and analyze the ethnomedicinal uses, bioactive constituents, and pharmacological activities of Ponciri Fructus. Various online bibliographic databases namely, SciFinder, PubMed, Google Scholar, and Web of Science were used for collecting information on traditional uses, biological activities, and bioactive constituents. Concerning ethnomedicinal uses, Ponciri Fructus is extensively used in traditional Korean, Chinese, and Kampo medicines to mitigate allergic reactions, inflammation, edema, digestive complications, respiratory problems, spleen-related problems, liver complications, neuronal pain, hyperlipidemia, rheumatoid arthritis, cardiovascular problems, hernia, sinusitis, and insomnia. Several studies have shown that Ponciri Fructus is a major source of diverse classes of bioactive compounds namely flavonoids, terpenoids, coumarins, phytosterols, and alkaloids. Several in vivo and in vitro pharmacological activity evaluations such as antidiabetic, anti-obesity, anti-inflammatory, antiallergic, antimelanogenic, gastroprotective, anticancer, and neuroprotective effects have been conducted from Ponciri Fructus. However, scientific investigations focusing on bioassay-guided isolation and identification of specific bioactive constituents are limited. Therefore, an in-depth scientific investigation of Ponciri Fructus focusing on bioassay-guided isolation, mechanism based pharmacological studies, pharmacokinetic studies, and evaluation of possible toxicities is necessary in the future.

Eclipta prostrata (L.) L. (Asteraceae): Ethnomedicinal Uses, Chemical Constituents, and Biological Activities.

Eclipta prostrata (L.) L. (Syn.: Eclipta alba (L.) Hassak, Family: Asteraceae) is an important medicinal plant in the tropical and subtropical regions. It is widely used in treating various diseases of skin, liver and stomach in India, Nepal, Bangladesh, and other countries. The main aim of this review was to collect and analyze the available information on traditional uses, phytoconstituents, and biological activities of E. prostrata. The scientific information was collected from the online bibliographic databases such as Scopus, MEDLINE/PubMed, Google Scholar, SciFinder, etc. and books and proceedings. The active phytochemicals were coumestan derivatives, phenolic acid derivatives, flavonoids, triterpenoid and steroid saponins, substituted thiophenes, etc. Various extracts and isolated compounds of E. prostrata showed a wide range of biological activities such as antimicrobial, anticancer, hepatoprotective, neuroprotective and hair growth promoting activities. Relatively a few studies have been performed to reveal the exact phytoconstituents responsible for their corresponding pharmacological activities. Future studies should focus on detailed mechanism based studies using animal models and clinical studies.