Comprehensive Review on Herbal Medicine: Emphasis on Current Therapy and Role of Phytoconstituents for Cancer Treatment.

INTRODUCTION: Cancer poses a significant public health challenge in both developed and developing nations, with a rising global incidence of patients facing the threat of death due to abnormal cell proliferation. AIM: Review explores the utilization of different parts of herbal medicinal plants and their active pharmaceutical constituents in the prevention and treatment of various types of cancer. METHODOLOGY: Various anticancer medicinal plants have been identified, demonstrating their therapeutic effects by inhibiting cancer-stimulating enzymes and hormones, activating DNA repair processes, boosting the synthesis of protective stimulants, reducing the formation of free radicals, and enhancing individual immunity. Data for this study were gathered from diverse online bibliographic and databases, including Google, Google Scholar, Mendeley, Springer Link, Research Gate, and PubMed. RESULT: Herbal drugs have a huge contribution to the inhibition of the progression of cancer.A large volume of clinical studies has reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL) of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. CONCLUSION: The latest medicines for the clinical purpose (Above 50 %) are derived from herbal products. Furthermore, combination of these herbs with nanotechnology shows promise in treating specific carcinomas.

Development, evaluation, pharmacokinetic and biodistribution estimation of resveratrol-loaded solid lipid nanoparticles for prostate cancer targeting.

BACKGROUND AND AIM: The study was to extend systemic circulation and biological half-life (t1/2) of trans-resveratrol (RSV) using solid lipid nanoparticles (RSV-SLN) to improve its anti-cancer potential. METHODS: RSV-SLN was prepared by solvent emulsification evaporation technique and proceeded for evaluation like particle size, PDI, zeta potential, in vitro release, in vitro cytotoxicity, cellular internalisation, haemolysis and erythrocyte membrane integrity, platelet aggregation and pharmacokinetic studies in rats. Moreover, cancer cells accumulation of RSV-SLN also needs to be evaluated for proving their targeting ability. RESULT: Prepared SLN showed 126.85 ± 12.09 nm particle size, -24.23 ± 3.27 mV Zeta potential and 74.67 ± 4.76%. release at 48 h and haemocompatible. The cellular internalisation image showed the SLN reach in a cytoplasm and nucleus of PC3 prostate cells. RSV-SLN exhibited high t1/2 (8.22 ± 1.36 h) and 7.19 ± 0.69 h MRT (Mean residence time) and lower clearance i.e. 286.42 ± 13.64 mL/min/kg. The bio-distribution of RSV-SLN was found to be extremely high in prostate cells and accumulate 7.56 times greater than that of RSV solution. CONCLUSION: The developed RSV-SLN can be applied as potential carrier for delivery of drug of chemotherapeutics at an extend systemic circulation and targeting efficiency at tumour site.

An inquest into regulatory mechanism of caveolin by ischemic preconditioning against orchidectomy-challenged rat heart.

Lower level of testosterone in men is related to major risks of cardiovascular diseases. This risk may increase due to the opening of mitochondrial permeability transition pore (mPTP). The mPTP is also regulated by ischemic preconditioning (IPC) and a membrane protein known as caveolin. The cardioprotective effect of IPC is the most effective methodologies used in testosterone deficiency. Daidzein (DDZ) a caveolin inhibitor shows cardioprotective action. The experiment has been designed to evaluate the pretreated DDZ effect in IPC-mediated cardioprotective action in orchidectomy (OCZ)-challenged rat heart. The experiment was designed on male Wistar rats with/without OCZ. The level of testosterone is decreased by OCZ which reduces general body growth. Isolated heart from normal and OCZ rat was tied up on Langendorff's perfused apparatus and followed by ischemic reperfusion (IR) and IPC cycle. To investigate the cardioprotective effect of DDZ in heart with testosterone deficiency, a total of nine groups, each consisting of six rats (n = 6) were as follows: Sham, IR, IPC, IPC + OCZ, IPC + DDZ, IPC + OCZ + DDZ, IPC + sodium nitrite, IPC + OCZ + sodium nitrite, IPC + OCZ + DDZ + sodium nitrite. Hemodynamic parameters, cellular injury (infarct size, LDH, CKMB and cardiac troponin-T), oxidative stress, mitochondrial function, integrity and immunoblot analysis were assessed for each group. The experimental data showed that DDZ potentiated IPC-mediated increase in the heart rate, left ventricular diastolic pressure, coronary flow; + dp/dtmax, and - dp/dtmax. The pretreated DDZ decreases the action of LDH and CKMB, myocyte size, cardiac collagen content, infarct size and ventricular fibrillation and attenuation in oxidative stress and mitochondrial dysfunction in OCZ-challenged rat heart in all sets of experiments. Sodium nitrite, a producer of nitric oxide (NO), enhanced potentiating effects of DDZ on IPC-mediated cardioprotection in OCZ-challenged rats. These observations show that the downregulation of caveolin through impaired opening of mPTP during reperfusion and caveolin might be a potential adjuvant to IPC against cardiac injury in OCZ-challenged rats.

Angiotensin (1-7) facilitates cardioprotection of ischemic preconditioning on ischemia-reperfusion-challenged rat heart.

Ischemic preconditioning (IPC) is one of the most promising strategies used to protect the myocardium from ischemia-reperfusion injury. Ang (1-7) exhibits cardioprotective activity; however, its therapeutic potential on IPC-induced cardioprotection has not been reported in ischemia-reperfusion injury till date. Therefore, the first set of experiment was designed to evaluate the direct effect of Ang (1-7), in perfusion medium, on cardioprotective activity of IPC in rat heart challenged to ischemia-reperfusion injury. In addition, the acute and chronic effects of pretreated Ang (1-7) were investigated on cardioprotection of IPC in ischemia-reperfusion-challenged hearts in subsequent sets of experiments. The results showed that Ang (1-7) potentiated the IPC-induced increase in coronary flow and heart rate, decrease in lactate dehydrogenase and creatine kinase activity, ventricular fibrillation, and infarct size in ischemia-reperfusion-challenged animals in direct and chronic sets of experiments. Further, Ang (1-7) enhanced the IPC-induced attenuation in mitochondrial dysfunction, oxidative stress, and apoptosis in ischemia-reperfusion-challenged hearts in both sets of experiments. A-779, Mas receptor antagonist, abrogated potentiation effects of Ang (1-7) on IPC-induced cardioprotection in ischemia-reperfusion-challenged rats in the above set of experiments. These observations indicate that Ang (1-7)/Mas receptor activation could be a potential adjuvant to IPC during ischemia-reperfusion-induced cardiac injury.

Dual combination of resveratrol and pterostilbene aqueous core nanocapsules for integrated prostate cancer targeting.

Aim: Development and evaluation of aqueous core nanocapsules (ACNs) of BCS-II-class drug like resveratrol (RSV) and pterostilbene (PTE) for prostate cancer.Materials & methods: Identify synergistic effects of molar ratios of RSV and PTE against PC-3 cell. Selected ratio of drugs was added to ACNs by double-emulsification-method using Box-Behnken design. Further, assessed for physicochemical characterization, release kinetics, compatibility, in vitro cytotoxicity, in vivo pharmacokinetic and biodistribution studies.Results: Selected 1:1 ratio of RSV and PTE had greatest synergy potential have smaller particle-size (128.1 ± 3.21 nm), zeta-potential (-22.12 ± 0.2 mV), 0.53 PDI, improved encapsulation (87% for RSV, 72% for PTE), stable, no systemic toxicity, high biodistributed/accumulated in prostate cells.Conclusion: ACNs exhibited high t1/2 (12.42 ± 1.92 hs) and 8.20 ± 8.21 hs Mean Residence Time and lower clearance, proving the high effectiveness for prostate cancer.

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Nanoemulsions a Delivery System in the Making for Tumor Targeting Therapeutics: Evaluation and Characterization to Meet Clinical Challenges.

Cancer is a complex disease characterized by the uncontrolled and unregulated growth of cells followed by invasion and proliferation from the site of origin to other sites of the body. Conventional chemotherapy largely kills rapidly expanding and dividing cancer cells by impairing DNA synthesis and mitosis. It is associated with various types of adverse effects ranging from simple nausea and appetite loss to serious ones like bone marrow depression and compromised immunity etc., due to their non-selectivity and inability to differentiate. The ideal feature of a delivery system is delivering the drug to the target place to achieve the most therapeutic impact while having the least toxicity. With the advent of novel drug delivery systems, it has been easier to deliver the drug to the target site. Utilizing new techniques and technology makes it a feasible approach to target cancer cells. Nanoemulsions are isotropic mixtures of transparent or translucent oil globules dispersed in an aqueous phase that is kinetically stable and supported by an interfacial coating of surfactant and co-surfactant molecules with droplet sizes in the nanometre range. Nanoemulsions are the delivery system of choice in case of cancer because of certain key attributes, including biodegradability, biocompatibility, large surface area nonimmunogenicity, and release behavior control. At the same time, nanoemulsions have been engineered for various reasons, including enhanced biological half-life, target-specific binding ability, and imaging capability at different therapy levels by modifying the characteristics of nanoemulsions. This review focuses on current cancer treatment challenges and the role of nanoemulsions in treating cancer with their production methods, characterization methods, application, and quality attributes, which would help them make it to the clinics where cancer treatment is going on.

Modulation of Angiotensin-II and Angiotensin 1-7 Levels Influences Cardiac Function in Myocardial Ischemia-reperfusion Injury.

The angiotensin-converting enzyme-2 (ACE-2) alters the pathophysiology of various fatal cardiovascular diseases, including ischemic heart disease, whereas angiotensin 1-7 (Ang 1-7) exerts a wide range of actions. The effects of ischemia-reperfusion (IR) injury include damage to myocardial tissue that initiates protease action, causing cardiac cell death. Angiotensin- II (Ang-II) contributes through the renin-angiotensin system (RAS) to the IR injury, whereas Ang 1-7 paradoxically exerts a protective effect through the same. Thus, the myocardial ischemic reperfusion injury (MIRI) may be altered by the RAS of the heart. This review paper focuses on ACE-2, angiotensin-converting enzyme (ACE), and Ang 1-7 regulation in the RAS of the heart in the pathophysiology of MIRI. The treatment in such conditions using ACE-2 activator, ACE inhibitor, and Ang-II antagonists may promote vascular functions as well as cardio- protection.

Recent Advancement in Synthesis and Bioactivities of 1,3,4-Oxadiazole.

Derivatives of 1,3,4-oxadiazole are effective in the treatment and cure of a wide range of diseases in medical chemistry, while industrial development has shown that they can be utilised as corrosion inhibitors and light-emitting diodes. The researchers discovered several promising synthetic strategies that created 1,3,4-oxadiazoles in extraordinarily high yields while using environmentally friendly methods. These compounds can potentially be used in a wide range of lifechanging applications. Stable isomeric oxadiazole forms of pleconaril, raltegravir, butalamine, fasiplon, oxolamine, and several other drugs are among the numerous potent and effective pharmaceuticals that are now on the market. Fasiplon, butalamine, raltegravir, and pleconaril treat HIV/AIDS patients. This article has attempted to bring attention to the chemistry and pharmacology of oxadiazole and its derivatives. Oxadiazole derivatives have been used extensively as prospective therapeutic agents in clinical research, and this has become standard practice. The use of biological and in-silico models has enabled scientists to identify more synthetic analogues of cancer prevention, antifungal, and anti-HIV medications. This article provides recent information regarding procedures for synthesizing 1,3,4-oxadiazoles and their biological actions on the body.

Natural Polyphenols in Cancer Management: Promising Role, Mechanisms, and Chemistry.

BACKGROUND: Although cancers emerge rapidly and cancer cells divide aggressively, which affects our vital organ systems. Recently, cancer treatments are targeted immune systems mediating intrinsic cellular mechanisms. Natural efficacious polyphenols have been exhibited to help prevent most cancers and reverse the progression of cancers. METHODS: Many resources have been used to know the promising role of polyphenols in preventing and treating cancers. The electronic databases include Science Direct, Google, Google Scholar, PubMed, and Scopus. The search was limited to the English language only. RESULTS: Polyphenols have been reported as anti-metastatic agents that explore the promising role of these compounds in cancer prevention. Such agents act through many signaling pathways, including PI3K/Akt and TNF-induced signaling pathways. The chemical modifications of polyphenols and the structure-activity relationships (SARs) between polyphenols and anti-cancer activities have also been discussed. CONCLUSION: Many research papers were reported to explain the anti-cancer potential of Polyphenols, The SARs between polyphenols and anti-cancer activities, which correlate structures of polyphenols with significant chemotherapeutic action. The mechanism of anti-cancer potential is to be added for searching for new anti-cancer natural products.

Nanostructured Lipid Carriers Mediated Drug Delivery to Posterior Segment of Eye and their In-Vivo Successes.

BACKGROUND: The disease of the posterior segment of the eye is a major concern worldwide, and it affects more than 300 million people and leads to serious visual deterioration. The current treatment available is invasive and leads to serious eye complications. These shortcomings and patient discomfort lead to poor patient compliance. In the last decade, Nanostructured lipid carriers (NLC) have established a remarkable milestone in the delivery of drug substances to the posterior segment of the eye. Additionally, NLC can reduce the clearance due to adhesive properties which are imparted due to nano-metric size. This attribute might reduce the adverse effects associated with intravitreal therapy and thus enhance therapeutic efficacy, eventually raising patient adherence to therapy. The current review provides an inclusive account of NLC as a carrier to target diseases of the posterior segment of the eye. OBJECTIVE: The review focuses on the various barrier encountered in the delivery of drugs to the posterior segment of the eye and the detail about the physicochemical property of drug substances that are considered to be suitable candidates for encapsulation to lipid carriers. Therefore, a plethora of literature has been included in this review. The review is an attempt to describe methods adopted for assessing the in-vivo behavior that strengthens the potential of NLC to treat the disease of the posterior segment of the eye. CONCLUSION: These NLC-based systems have proven to be a promising alternative in place of invasive intravitreal injections with improved patient compliance.

Anti-Inflammatory and Antimicrobial Potential of 1, 3, 4-Oxadiazoles and its Derivatives: A Review.

1, 3, 4-oxadiazole and its derivatives have significant anti-inflammatory and antimicrobial property. Their precise mechanism of action is not known but it is postulated that they act by inhibiting the biosynthesis of certain prostaglandins. 1, 3, 4-oxadiazoles are a class of heterocyclic compounds with wide variety of biological and pharmacological activities. They have been reported to possess analgesic, antimicrobial, antipyretic and anti-inflammatory properties. These compounds are also active against a number of other inflammatory conditions such as arthritis, gout etc. A wide variety of these compounds have been synthesized and some of them are under clinical trials. In this review article, anti-inflammatory and antimicrobial activity of the 1, 3, 4- oxadiazole shall be discussed.

Role of vitamin D in management of diabetes and unresolved cardiovascular diseases.

BACKGROUND: Vitamin D deficiency is becoming a widely recognized global health issue. Serum values of 25(OH) vitamin D (<20 ng/ml) are used to identify vitamin D deficiency. By prompting vascular endothelial cells to activate their nuclear receptor in cardio-myocytes, Vitamin D regulates obesity, Renin-angiotensin system (RAS), energy consumption, and pancreatic cell function. Vitamin D deficiency has been associated with diabetes, asthma, hyperlipidaemia, and pulmonary hypertension in humans. METHODS: PubMed and Google Scholar databases were utilised to search the literature on vitamin D and related diseases. RESULT: It is also linked to an elevated risk of death and heart disease. On the other hand, meta-analyses of vitamin D intervention and trials have found no substantial changes in insulin sensitivity, lipid markers, or blood pressure, which result in the association between deficiency of vitamin D and cardiovascular disease. CONCLUSION: In this review, we present the most recent research on the effects of Vitamin D therapy on various cardiovascular diseases and diabetes, and explain the underlying mechanisms.

A Review on Novel Synthesis Approaches and Biological Activities of 1,2,4- Oxadiazole and 1,3,4-Oxadiazole Tailored Compounds.

Rational design and synthesis of novel compounds with both effectivity and safety properties have always been a formidable task in the development of drugs. Oxadiazoles are heterocyclic bioscaffolds occurring as motifs in drug-like molecules. This review article highlights comprehensive and systematic information of compounds containing 1,2,4-oxadiazoles and 1,3,4-oxadiazole rings. The routes for the synthesis of the oxadiazoles have also been discussed, along with their biological significance. This review may help researchers in rational design for the development of effective and less toxic 1,3,4- oxadiazole based compounds. We present an informative review about the drugs derived from oxadiazole rings and their therapeutic application as well as a brief remark on the future development prospects.

Caveolins: Expression of Regulating Systemic Physiological Functions in Various Predicaments.

Caveolins are membrane proteins which contains caveolae. They are present in the plasma membrane. Many researchers found that caveolae have been associated with expression of the caveolins in major physiological networks of mammalian cells. Subtypes of caveolin including caveolin-1 and caveolin-2 have been found in micro arteries of rat brain, while caveolin-3 has been found in astrocytes. Caveolin-1 and caveolae play important roles in Alzheimer's disease, cancer, ischemic preconditioning-mediated cardio-protection, postmenopausal alterations in women, and age-related neurodegeneration. Caveolin-1 may modify fatty acid transmembrane flux in adipocytes. The discovery of a link between ischemia preconditioning, cardio-protection, and endothelial nitric oxide synthase has supported cardiovascular research tremendously. Therefore, caveolins are effective in regulation of cellular, cardiovascular, brain, and immune processes. They ascertain new signalling pathways and link the functionalities of these pathways. This review paper focuses on contribution of caveolins in various conditions, caveolin expression at the molecular level and their physiological effects in many organ systems.

Time-frequency analysis and fuzzy-based detection of heat-stressed sleep EEG spectra.

Nowadays, sleep disorders are contemplated as the major issue in the human lives. The current work aims at extraction of time-frequency information from recorded dataset and provides an efficient sleep stage detection method. Recordings of brain signal namely electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) were carried out under defined clinical condition for the classification of sleep EEG. Subsequent upon the extraction of various features from the raw EEG data, neuro-fuzzy system is trained to classify the sleep stages into three major classes namely awake, slow wave sleep (SWS), and rapid eye movement sleep (REM). This classification would enable medical professionals to diagnose sleep related disorders accurately. The results obtained clearly indicate that the mean performance for SWS stage is profound as compared to REM and awake stage. Specificity and sensitivity of the proposed method are obtained as 95.4% and 80%, respectively. The average accuracy of the system employing neuro-fuzzy approach is found to be 90.6% in which SWS stage was best detected among the other stages of sleep EEG.Graphical abstract.

Invasomes for Enhanced Delivery through the Skin: Evaluation of Systems to Meet with Clinical Challenges.

BACKGROUND: Portage of therapeutic agents directly to the skin (cutaneous/dermal delivery) is the preferable approach in mitigating and curing a variety of skin manifestations, including itching, eczema, acne, psoriasis keratinization, and skin cancer. Dermal delivery reduces side effects associated with systemic therapy and allows maximum utilization of the available doses. Invasomes are the next generation of liposomes with greater flexibility, elasticity, and permeability through the skin than liposomes and ethosomes. OBJECTIVE: This review article highlights various aspects of invasomes, including the structure and composition of invasomes, methods of preparation of invasomes, the mechanism involved in better penetration through the skin, key parameters to be considered for effective permeation, therapeutic applications of invasomes as novel drug delivery systems, and future development and challenges. METHODS: The authors have reviewed various primary and secondary sources, including PUBMED, SCIENCE DIRECT, INFORMA, and patents.com, to collect information on various aspects of invasomes. RESULTS AND CONCLUSION: Invasomes are novel vesicular drug delivery systems that have been used for dermal delivery of drugs for various therapeutic applications. These novel carriers have great ability, and their properties can be highly modulated by varying their composition and concentration of terpenes. Based on all the research reports gathered, it is well proven that these systems have a much higher potential for delivering drugs for skin manifestations and could expand the opportunities for treating various dermatological issues, increasing day by day.

Mechanistic Pathways of ATP Sensitive Potassium Channels Referring to Cardio-Protective Effects and Cellular Functions.

A study of potassium channels correlates the fundamentals of mechanistic pathways and various physiological functions. The knowledge of these pathways provides the background, how to determine unit cell functions and to affect cardio protection. ATP sensitive potassium channels adjust excitability of membrane and functions as per metabolic status of cell. A lot of energy consumption primarily occurred in skeletal muscles which also express high number of potassium channels. The increase in calcium release and high heat production is occurred due to loss of potassium channels. Such type of mediations determines metabolic changes and energy required in the dissipation. IPC reduces infarct size in anesthetized mice. In ischemic-reperfusion, pressure in left ventricle was watched while contractile power recovery did not happen. It was seen that elements of intact potassium channel are fundamental for Ischemic preconditioning (IPC). If more prominent is enactment of potassium channels and their cardiologic effects create high heart rate. All the more as of late, it has been suggested that mitochondrial ATP sensitive potassium channels are critical as closing stage effectors which trigger IPC as opposed to sarcolemmal potassium channels. Nevertheless, the importance of the potassium channels reconsidered in cardio-protection in present findings. These discoveries recommend that potassium channels in the adjusting ischemic-reperfusion damage in mice. The heart rate of the mouse occurred during ischemia; enhance watchful extrapolation applied to larger warm blooded animals.

Ceiling effect of Postconditioning and Atrial Natriuretic Peptide in Cardioprotection against Ischemia Reperfusion Injury in Ovariectomized rat hearts

Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff's apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.

Neural network-based evaluation of chronic non-thermal effects of modulated 2450 MHz microwave radiation on electroencephalogram.

The effects of chronic exposure (2 h daily for 21 days) of 1 kHz square wave-modulated 2450 MHz microwave radiation (non-thermal) on sleep-EEG, open field behavior, and thyroid hormones (T(3), T(4), and TSH) have been analyzed in an animal model. Results revealed significant changes in these pathophysiological parameters (p < 0.05 or better), except body temperature, grooming behavior, and TSH levels. The sleep-EEG power spectrum data for slow wave sleep (SWS), rapid eye movement (REM) sleep, and awake (AWA) states in two experimental groups of rats (microwave exposed and the control) were tested by an artificial neural network (ANN), containing 60 nodes in input layer, weighted from power spectrum data from 0 to 30 Hz, 18 nodes in hidden layer and an output node. The target output values for this network were determined with another five-layered neural network (with the structure of 6-14-1-14-6). The input and output of this network was assigned with the six confirmed pathophysiological changes. The most important feature for chronic exposure of 2450 MHz microwave exposure and for control subjects was extracted from the third layer single neuron and used as the target value for the three-layered ANN. The network was found effective in recognizing the EEG power spectra with an average of 71.93% for microwave exposure and 93.13% for control subjects, respectively. However, the lower percentage of pattern identification agreement in the microwave-exposed group in comparison to the control group suggest only mild effects of microwave exposure with this experimental setup.