Fermented formulation of Silybum marianum seeds: Optimization, heavy metal analysis, and hepatoprotective assessment.

BACKGROUND: Fermented formulations are extensively used in Ayurveda due to several benefits like improved palatability, bioavailability, pharmacological potential, and shelf life. These formulations can also quench the heavy metals from the plant material and thus reduce the toxicity. Seeds of Silybum marianum (L.) Gaertn. are widely used for the management of many liver diseases. STUDY DESIGN AND METHODS: In the present study, we developed a novel fermented formulation of S. marianum seeds and evaluated parameters like safety (heavy metal analysis) and effectiveness (hepatoprotective). As the developed formulation's validation is crucial, the critical process variables (time, pH, and sugar concentration) are optimized for alcohol and silybin content using the Box-Behnken design (BBD). RESULTS: The response surface methodology coupled with BBD predicted the optimized conditions (fermentation time (28 days), pH 5.6, and sugar concentration (22.04%)) for the development of a fermented formulation of the selected herb. Moreover, the alcohol content (6.5 ± 0.9%) and silybin concentration (26.1 ± 2.1%) were confirmed in optimized formulation by GC-MS and HPTLC analysis. The optimized formulation was also analyzed for heavy metals (Pb, As, Hg, and Cd); their concentration is significantly less than the decoction of herbs. Further, the comparative evaluation of the developed formulation with the marketed formulation also confirmed that the fermented formulation's silybin concentration and percentage release were significantly enhanced. In addition, the developed fermented formulation's percentage recovery of HepG2 cell lines after treatment with CCl4 was significantly improved compared with the marketed formulation. CONCLUSION: It can be summarized that the developed fermented formulation improves safety and effectiveness compared to other market formulations. Finally, it can be concluded that the developed fermented formulation could be further explored as a better alternative for developing Silybum marianum preparation.

Exploring the Prospective of Curcumin-loaded Nanomedicine in Brain Cancer Therapy: An Overview of Recent Updates and Patented Nanoformulations.

Cancer is a complex, one of the fatal non-communicable diseases, and its treatment has enormous challenges, with variable efficacy of traditional anti-cancer agents. By 2025, it is expected that 420 million additional cases of cancer will be diagnosed yearly. However, among various types of cancer, brain cancer treatment is most difficult due to the presence of blood-brain barriers. Nowadays, phytoconstituents are gaining popularity because of their biosafety and low toxicity to healthy cells. This article reviews various aspects related to curcumin for brain cancer therapeutics, including epidemiology, the role of nanotechnology, and various challenges for development and clinical trials. Furthermore, it elaborates on the prospects of curcumin for brain cancer therapeutics. In this article, our objective is to illuminate the anti-cancer potential of curcumin for brain cancer therapy. Moreover, it also explores how to defeat its constraints of clinical application because of poor bioavailability, stability, and rapid metabolism. This review also emphasizes the possibility of curcumin for the cure of brain cancer using cuttingedge biotechnological methods based on nanomedicine. This review further highlights the recent patents on curcumin-loaded nanoformulations for brain cancer. Overall, this article provides an overview of curcumin's potential in brain cancer therapy by considering challenges to be overwhelmed and future prospective. Moreover, this review summarizes the reported literature on the latest research related to the utility of curcumin in brain cancer therapy and aims to provide a reference for advanced investigation on brain cancer treatment.

Fabrication of Sustained Release Curcumin-Loaded Solid Lipid Nanoparticles (Cur-SLNs) as a Potential Drug Delivery System for the Treatment of Lung Cancer: Optimization of Formulation and In Vitro Biological Evaluation.

The goal of current research was to develop a new form of effective drug, curcumin-loaded solid lipid nanoparticles (Cur-SLNs) and test its efficacy in the treatment of lung cancer. Different batches of SLNs were prepared by the emulsification-ultrasonication method. For the optimization of formulation, each batch was evaluated for particle size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). The formulation components and process parameters largely affected the quality of SLNs. The SLNs obtained with particle size, 114.9 ± 1.36 nm; PI, 0.112 ± 0.005; ZP, -32.3 ± 0.30 mV; EE, 69.74 ± 2.03%, and DL, 0.81 ± 0.04% was designated as an optimized formulation. The formulation was freeze-dried to remove excess water to improve the physical stability. Freeze-dried Cur-SLNs showed 99.32% of drug release and demonstrated a burst effect trailed by sustained release up to 120 h periods. The erythrocyte toxicity study of Cur-SLNs and its components demonstrated moderate hemolytic potential towards red blood cells (RBCs). The cytotoxic potential of the formulation and plain curcumin was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against A549 cell line. After 48 h of incubation, Cur-SLNs demonstrated more cytotoxicity (IC50 = 26.12 ± 1.24 µM) than plain curcumin (IC50 = 35.12 ± 2.33 µM). Moreover, the cellular uptake of curcumin was found to be significantly higher from Cur-SLNs (682.08 ± 6.33 ng/µg) compared to plain curcumin (162.4 ± 4.2 ng/µg). Additionally, the optimized formulation was found to be stable over the period of 90 days of storage. Hence, curcumin-loaded SLNs can be prepared using the proposed cost effective method, and can be utilized as an effective drug delivery system for the treatment of lung cancer, provided in vivo studies warrant a similar outcome.

Green approach for the recovery of secondary metabolites from the roots of Nardostachys Jatamansi (D. Don) DC using microwave radiations: Process optimization and anti-alzheimer evaluation.

Nardostachys jatamansi (D. Don) DC is a highly valued medicinal herb that has been used in traditional medicinal systems for its remedial effects. Owing to the over-exploitation and unethical trade of N. jatamansi, the accelerating global demand of herbal products from this plant cannot be satisfied by the conventional extraction approach. In view of the progressive demand and incredible biological potential of herb, the present research was designed to optimize various extraction parameters for microwave-assisted extraction (MAE). The extracts obtained from the traditional and green approach were also assessed for the recovery of secondary metabolites and anti-Alzheimer's potential. Various parameters like microwave power, temperature, and time of irradiation were optimized for MAE using Box Behkhen Design (BBD) The scanning electron microscopy of different plant samples was also done to observe the effect of microwave radiations. Further, the metabolite profiling of different extracts was also done by gas chromatography-mass spectrometry (GC-MS) analysis. Also the different behavioral and biochemical parameters along with acetylcholinesterase (AChE) inhibitory potential were assessed to evaluate the anti-Alzheimer's potential. Optimized parameters for MAE were found to be as microwave power 187.04 W, temperature 90°C, and irradiation time 20 min. The extract yield in MAE was significantly enhanced as compared to the conventional method. Also, the total phenolic content and total flavonoid content (TFC) were improved pointedly from 32.13 ± 0.55 to 72.83 ± 1.1 mg of GAE/g of extract and 21.7 ± 0.85 to 39.21 ± 0.7 mg of RUE/g of extract respectively. Later, the GC-MS analysis of various extracts confirmed the enhancement in the concentration of various sesquiterpenes like jatamansone, spirojatamol, valerenal, valeric acid, globulol, nootkatone and steroidal compounds such as sitosterol, ergosterol, stigmastanone, etc. in the optimized extract. A significant improvement in anti-Alzheimer's potential was also observed owing to the better concentration of secondary metabolites in the optimized microwave extract. From the current findings, it could be concluded that the MAE could be a successful and green alternative for the extraction and recovery of secondary metabolites from the selected medicinal herb.

Evaluation of Ulcer Protective Activity of Morus alba L. Extract-Loaded Chitosan Microspheres in Ethanol-Induced Ulcer in Rat Model.

Due to an unhealthy lifestyle, gastric ulcers have become a very common disease these days. Moreover, the side effects linked with the prolonged use of conventional treatments have shifted the paradigm towards herbal therapies. The leaves of Morus alba L. (Family-Moraceae) have been traditionally used for a large number of metabolic diseases. In the present research, we focused on the development of chitosan microspheres using extracts of leaves of Morus alba L. and their evaluation for gastroprotective efficacy against ethanol-induced ulcers in experimental rats. The process of development of M. alba extract microsphere (MEM) is also optimized using the Box-Behnken design. The formulation was prepared at optimized conditions (chitosan concentration (1.66% w/w), volume of glutaraldehyde (4.69 mL), and stirrer rotation per minute, RPM, 854.8), and the percentage yield (Y 1) of the resulted microspheres is ∼95% with an encapsulation efficiency (EE) of (Y 2(rutin)) ∼86%, Y 2(quercetin)) ∼85%, and particle size (Y 3) of ∼40 µm. The MEM prepared at optimized conditions can also be characterized for various parameters to ensure the uniformity of parameters. Also, the drug release studies indicated that the percentage release of rutin and quercetin from MEM was enhanced as compared to M. alba extract (ME) alone. Furthermore, in vivo analysis of the antiulcer potential of pretreatment with ME and MEM (500 mg/kg p.o.) in rats indicated that mucosal lesions, gastric juice volume, and total acidity were significantly altered as compared to ethanol-treated animals. Histopathology of tissue sections also confirmed the protection of gastric mucosa on pretreatment with MEM at 500 mg/kg p.o. On the basis of these findings, we can conclude that prepared microspheres can be used to develop a sustained release formulation of extract for the management of gastric ulcers. However, additional research is needed to establish the specific mechanisms of M. alba's antiulcer efficacy.

Mechanistic Insights into the Pharmacological Significance of Silymarin.

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, ß-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

Mutivariate optimization strategy for the sonication-based extraction of Nardostachys jatamansi roots and analysis for chemical composition, anti-oxidant and acetylcholinesterase inhibitory potential.

Extracts from medicinal plants are generally obtained by conventional methods like percolation and maceration. Owing to limitations of traditional methods and to meet the rising demand of extracts, the development of new green approaches is need of hour. In the present research, we have developed an ultrasound-assisted extraction (UAE) method for the Nardostachys jatamansi (NJ) D. Don, DC roots and optimized the extraction parameters for possible improved extract yield. A multivariate optimization strategy using the Centre Composite Design coupled with response surface methodology was applied. A numerical optimization approach accurately predicted the extraction conditions (sonication time âˆ¼ 20 min, ethanol âˆ¼ 70 % and a liquid/solid ratio of about 21:1). Scanning electron microscopy of the plant samples after UAE also indicated the cavitation effect due to sound waves. GC-MS analysis of the optimized ultrasound extract (OUNJ) confirmed improvement in the concentration of various secondary metabolites like jatamansone (91.8 % increase), spirojatamol (42.3 % increase), globulol (130.4 % increase), sitosterol (84.6 % increase) as compared to the soxhlet extract (SXNJ). Different anti-oxidant parameters (DPPH, Glutathione, Catalase SOD and NO) were also significantly altered (p < 0.05) in the optimized extracts. The IC50 to inhibit acetylcholinesterase activity (AChE) in vitro and its concentration in brain homogenates were significantly (p < 0.05) improved by OUNJ extract as compared to the SXNJ ones. To conclude, we can say that established optimized conditions for UAE of N. jatamansi roots not only reduce the extraction time but also improved the pharmacological potential of the extracts.

Neurobehavioral and Biochemical Evidences in Support of Protective Effect of Marrubiin (Furan Labdane Diterpene) from Marrubium vulgare Linn. and Its Extracts after Traumatic Brain Injury in Experimental Mice.

Traumatic brain injuries due to sudden accidents cause major physical and mental health problems and are one of the main reasons behind the mortality and disability of patients. Research on alternate natural sources could be a boon for the rehabilitation of poor TBI patients. The literature indicates the Marrubium vulgare Linn. and its secondary metabolite marrubiin (furan labdane diterpene) possess various pharmacological properties such as vasorelaxant, calcium channel blocker, antioxidant, and antiedematogenic activities. Hence, in the present research, both marrubiin and hydroalcoholic extracts of the plant were evaluated for their neuroprotective effect after TBI. The neurological severity score and oxidative stress parameters are significantly altered by the test samples. Moreover, the neurotransmitter analysis indicated a significant change in GABA and glutamate. The histopathological study also supported the observed results. The improved neuroprotective potential of the extract could be attributed to the presence of a large number of secondary metabolites including marrubiin.

Application of Green Technologies in Design-Based Extraction of Celastrus paniculatus (Jyotishmati) Seeds, SEM, GC-MS Analysis, and Evaluation for Memory Enhancing Potential.

Background: The Celastrus paniculatus (CP), commonly known as Jyotishmati, is considered as "elixir of life" by Indian people for the prevention or management of many ailments. The seed powder and its extract have widely used commercially for the preparation of various Ayurvedic formulations for the improvement of memory. CP seeds were generally extracted by conventional extraction methods (CEMs) which are assumed to impact environment burden and also produce low extract yield. Green extraction with possible improvement in extract yield has always been the need of hour for selected medicinal plant. Objective: In the present research, we aimed to optimize the different extraction factors in microwave and ultrasound-based extraction. The various extracts obtained in conventional and green methods are also evaluated for the possible improvement in memory enhancing potential. Materials and Methods: The selected medicinal herb was extracted by CEM (maceration and percolation). In green methods such microwave-assisted extraction (MAE) and ultrasound assisted-extraction (UAE), various parameters were optimized using Box-Behnken design coupled with response surface methodology. The scanning electron microscopy (SEM) and gas chromatography-mass spectroscopy (GC-MS) analyses were also done to confirm the possible improvement in concentration of plant actives. The Swiss albino mice were used to evaluate memory enhancing potential of different extracts. Results: At the optimized conditions MAE and UAE the extraction yield, total phenolic content (TPC) and Total flavonoid content (TFC) are significantly improved. The GC-MS analysis further confirms the improvement in concentration of certain fatty acid esters, pilocarpine, and steroidal compounds in optimized extracts. The optimized extracts also exhibited the significant improvement in behavioral parameters, oxidative stress-induced parameters, and acetylcholinesterase inhibitory potential. Discussion and Conclusion: From the results, we can say that the application of green technologies in design-based extraction of selected herb not only significantly reduces the extraction time but also improves the extract yield and concentration of plant actives. In nutshell, it can be concluded that the green approaches for extraction of seeds of Celastrus paniculatus could be scale up at a commercial level to meet the rising demand for herbal extract.

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.

Exploration of therapeutic applicability and different signaling mechanism of various phytopharmacological agents for treatment of breast cancer.

BACKGROUND: Cancer is one of the most dreaded diseases characterized by uncontrolled proliferation of abnormal cells that occurs due to impairment of cell division and apoptosis process. Cancer is categorized into several types on the basis of affected organs and breast cancer (BC) is the most predominant cause of mortality among women. Although, several synthetic and semi-synthetic therapies have been developed for the treatment of BC but they exhibit numerous serious adverse effects therefore; pharmacological agents with fewer/no side effects need to be explored. Plants and phytoconstituents perhaps fulfill the aforementioned requirement and could serve as a potential and alternative therapy for BC treatment. The ongoing biomedical research, clinical trials and number of patents granted have further boosted the acceptance of the plants and plant-derived constituents in the effective treatment of BC. PURPOSE OF STUDY: Various treatment strategies such as checkpoint inhibitors, targeting micro RNA, apoptotic pathway, BRCA-1 gene, P53 protein, P13K/Akt/mTOR pathway, notch signaling pathway, hedgehog/gli-1 signaling pathway, poly-ADP ribose polymerase inhibitors, mitogen-activated protein kinase inhibitors etc. are available for BC. In addition to these synthetic and semi-synthetic drug therapies, several natural constituents such as alkaloids, sesquiterpenes, polyphenols, flavonoids and diterpenoids from medicinal plants, vegetables and fruits are reported to possess promising anti-cancer activity. The purpose of the present review is to highlight the various signaling pathways through which plants/herbs show the anti-cancer potential especially against the BC. STUDY DESIGN: The literature for the present study was collected from various databases such as Pubmed, Scopus, Chemical Abstracts, Medicinal and aromatic plant abstracts, Web of Science etc. The different patent databases were also reviewed for the anti-cancer (BC) potential of the particular herbs/plants and their formulations. RESULT AND CONCLUSION: In this review, we have discussed the number of plants along with their patents of different herbal formulations which are being used for the treatment of BC and other types of cancers. We have also delineated the different signaling mechanisms through which they inhibit the growth of BC cells. In nutshell, we can conclude that large numbers of herbs or their extracts are reported for the treatment of BC. But still, there is further need for research in-depth to translate the use of natural products clinically BC treatment.

Bioactive compounds and their libraries: An insight into prospective phytotherapeutics approach for oral mucocutaneous cancers.

Oral mucocutaneous cancers (OMCs) are cancers that affect both the oral mucosa and perioral cutaneous structures. Common OMCs are squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and malignant melanoma (MM). Anatomical similarities and conventions which categorizes these lesions blur the magnitude of OMCs in diverse populations. The burden of OMC is high in the sub-Saharan Africa and Indian subcontinents, and the cost of management is prohibitive in the resource-limited, developing world. Hence, there is a pressing demand for the use of cost-effective in silico approaches to identify diagnostic tools and treatment targets for diseases with high burdens in these regions. Due to their ubiquitousness and accessibility, the use of therapeutic efficacy of plant bioactive compounds in the management of OMC is both appropriate and plausible. Furthermore, screening known mechanistic disease targets with well annotated plant bioactive compound libraries is poised to improve the routine management of OMCs provided that the requisite access to database resources are available and accessible. Using natural products minimizes the side effects and morbidities associated with conventional therapies. The development of innovative treatments approaches would tremendously benefit the African and Indian populace and reduce the mortalities associated with OMCs in the developing world. Hence, we discuss herein, the potential benefits, opportunities and challenges of using bioactive compound libraries in the management of OMCs.

Ageratum conyzoides L. and Its Secondary Metabolites in the Management of Different Fungal Pathogens.

Ageratum conyzoides L. (Family-Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant's dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discovery.

Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers.

Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase ß (IκKß), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines.

Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is a gradually growing irreversible illness of the brain that almost affects every fifth person (aged > 80 years) in the world. World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030. The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder. Natural inhibitors of acetylcholine (ACh) such as galanthamine and rivastigmine are used commercially in the treatmentof AD. The biomolecules such assesquiterpenes, possess a great structural diversity and are responsible for a plethora of pharmacological properties. The potential of various sesquiterpenes as anticholinesterase has been reviewed in this article. For this purpose, the various databases, mainly PubMed, Scopus, and Web of Science were investigatedwith different keywords such as "sesquiterpenes+acetylcholinesterase" and "sesquiterpenes+cholinesterase+inhibitors" in the surveyed time frame (2010-2020). A vast literature was evident in the last decade, which affirms the potential of various sesquiterpenes in the improvement of cholinergic transmission by inhibiting the AChE. After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9µM and can be considered as potential candidates for the improvement of learning and memory. Sesquiterpene is an important category of terpenoids, found to possess a large spectrum of biological activities. The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol,etc) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD.

Statistically Designed Extraction of Herbs Using Ultrasound Waves: A Review.

BACKGROUND: Extraction is the foremost step to isolate the natural constituents from a medicinal plant and leads the process of development of herbal formulation from bench to bed. INTRODUCTION: In the field of extraction, the optimization approach helps in achieving better yield and quality where a response of concern is determined or influenced by various variables. This review aimed at congregating the application of different statistical designs (CCD/BBD) to optimize the Ultrasound assisted extraction (UAE) parameters for the recovery of various plant actives belonging to different categories. METHODOLOGY: The literature published during the last decade in the various reputed databases (Web of Science, Pubmed, Scopus) was reviewed and compiled to reveal the role of response surface methodology in optimizing the influential parameters involved in the ultrasound assisted extraction of herbs. CONCLUSION: From the present investigations, it can be concluded that the different variables, such as sonication power, temperature, time, solute to solvent ratio are generally optimized in UAE of herbs. Moreover, it has also been evidenced from the review of published data that the flavonoids/phenolic acids (>50%) leads the race for the extraction of plants using sound waves. It can be said that the statistically designed UAE has a vast prospective in bringing about a green mutiny in the herbal drug industry and the modeling of various parameters shall be able to absolutely build up a complete drug innovation course (bench to bed).

Recent Patents on Phytoconstituents-based Formulations for the Treatment of Acne Infection: A Review.

BACKGROUND: Acne is an infection of the skin that occurs in both men and women during their lifespan. There are various natural or synthetic products available in the market to prevent and cure this disease. INTRODUCTION: The majority of the world population depends on the herbs or natural resources for the relief of acne disease. These are used to lessen the cost of treatment and the side effects of synthetic analogs. METHODS: We have explored the various authentic web resources to compile information regarding different patented and marketed herbal formulations for acne treatment. RESULTS: It has been found that most of the herbal formulation for acne include the plant actives/extracts having the potential activity against the Propionibacterium acne. The occurrence of this skin disease is also associated with the presence of free radicals in the body, which also causes the inflammation and redness of the skin. Further, the study of various patents also revealed that herbs with anti-oxidant properties have been used in most of the herbal anti-acne formulations. Moreover, the various patents also give the idea that herbal formulations also prevent the appearance of pimples on the skin. CONCLUSION: It has been concluded that the herbal anti-acne formulation is not only used to treat acne but also prevents this disease safely and economically.

Encapsulation of babchi essential oil into microsponges: Physicochemical properties, cytotoxic evaluation and anti-microbial activity.

Babchi essential oil (BEO) is a valuable essential oil reported to possess a variety of biological activities such as antitumor, anti inflammatory, immunomodulatory, antioxidant, antifungal and antibacterial properties. Due to its anti-microbial properties, this oil possesses an immense potential for the treatment of dermatological disorders. Further, it has minimal tendency to develop resistance, a common issue with most of the antibiotics. However, its highly viscous nature and poor stability in the presence of light, air and high temperature, limits its practical applications. To surmount these issues, this research aims to encapsulate BEO in ethyl cellulose (EC) microsponges for enhanced stability, antibacterial effect and decreased dermal toxicity. The quasi emulsion solvent evaporation technique was used for fabrication of the BEO microsponges employing EC as polymer, polyvinyl alcohol (PVA) as stabilizer and dichloro methane (DCM) as solvent. The effect of formulation variables such as the amount of EC and PVA were also investigated. The prepared microformulations were evaluated for production yield, encapsulation efficiency, particle size and in vitro release. In vitro cytotoxicity was also checked to assess dermal safety of BEO microsponges. Results revealed that all the dispersions were in micro size range (20.44 ± 3.13 µm to 41.75 ± 3.65 µm), with good encapsulation efficiency (87.70 ± 1.20% of F2) and controlled release profile (cumulative drug release 73.34 ± 1.76%). Field emission scanning electron microscopy results showed that the microsponges possessed a spherical uniform shape with a spongy structure. Results of cytotoxicity study indicated that the prepared microsponges were safer on dermal cells in comparison to pure BEO. The optimized formulation was also evaluated for in vitro antimicrobial assay against dermal bacteria like Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, which confirmed their enhanced antibacterial activity. Furthermore, the results of photostability and stability analysis indicated improved stability of BEO loaded microsponges. Hence, encapsulation of BEO in microsponges resulted in efficacious carrier system in terms of stability as well as safety of this essential oil alongwith handling benefits.

Intensification of marrubiin concentration by optimization of microwave-assisted (low CO2 yielding) extraction process for Marrubium vulgare using central composite design and antioxidant evaluation.

CONTEXT: Marrubium vulgare Linn (Lamiaceae) was generally extracted by conventional methods with low yield of marrubiin; these processes were not considered environment friendly. OBJECTIVE: This study extracts the whole plant of M. vulgare by microwave assisted extraction (MAE) and optimizes the effect of various extraction parameters on the marrubiin yield by using Central Composite Design (CCD). MATERIALS AND METHODS: The selected medicinal plant was extracted using ethanol: water (1:1) as solvent by MAE. The plant material was also extracted using a Soxhlet and the various extracts were analyzed by HPTLC to quantify the marrubiin concentration. RESULTS: The optimized conditions for the microwave-assisted extraction of selected medicinal plant was microwave power of 539 W, irradiation time of 373 s and solvent to drug ratio, 32 mL per g of the drug. The marrubiin concentration in MAE almost doubled relative to the traditional method (0.69 ± 0.08 to 1.35 ± 0.04%). The IC50 for DPPH was reduced to 66.28 ± 0.6 µg/mL as compared to conventional extract (84.14 ± 0.7 µg/mL). The scanning electron micrographs of the treated and untreated drug samples further support the results. DISCUSSION AND CONCLUSION: The CCD can be successfully applied to optimize the extraction parameters (MAE) for M. vulgare. Moreover, in terms of environmental impact, the MAE technique could be assumed as a 'Green approach' because the MAE approach for extraction of plant released only 92.3 g of CO2 as compared to 3207.6 g CO2 using the Soxhlet method of extraction.

Self emulsifying drug delivery system (SEDDS) for phytoconstituents: a review.

The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/ derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued were reviewed using different databases such as PubMed, Google Scholar, Google patents, Scopus and Web of Science. In a nutshell, we can say that SEDDS was established as a novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products.