Investigations of Limeum Indicum Plant for Diabetes Mellitus and Alzheimer's Disease Dual Therapy: Phytochemical, GC-MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In-Vivo Studies.

Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer's disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against α-, ß-glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO-A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against α-glucosidase (IC50=68.47±0.05 µg/mL), methanol extract against ß-glucosidase (IC50=91.12±0.07 µg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 µg/mL), ethanol extract against BChE (28.41±0.01 µg/mL), n-hexane fraction against MAO-A (IC50=150.5±0.31 µg/mL) and methanol extract for MAO-B (IC50=75.95±0.13 µg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in-vivo investigation, ethanol extract produced hypoglycemic effect (134.52±2.79 and 119.38±1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in-vivo studies.

Managing Weed-Crop Interactions Enhances Chickpea (Cicer arietinum L.) Chemical Components.

Chickpea (Cicer arietinum L.) is a major pulse crop worldwide, renowned for its nutritional richness and adaptability. Weeds are the main biotic factor deteriorating chickpea yield and nutritional quality, especially Asphodelus tenuifolius Cav. The present study concerns a two-year (2018-19 and 2019-20) field trial aiming at evaluating the effect of weed management on chickpea grain quality. Several weed management practices have been here implemented under a factorial randomized complete block design, including the application of four herbicides [bromoxynil (C7H3Br2NO) + MCPA (Methyl-chlorophenoxyacetic acid) (C9H9ClO3), fluroxypyr + MCPA, fenoxaprop-p-ethyl (C18H16ClNO5), pendimethalin (C13H19N3O4)], the extracts from two allelopathic weeds (Sorghum halepense and Cyperus rotundus), two mulches (wheat straw and eucalyptus leaves), a combination of A. tenuifolius extract and pendimethalin, and an untreated check (control). Chickpea grain quality was measured in terms of nitrogen, crude protein, crude fat, ash, and oil content. The herbicides pendimethalin (Stomp 330 EC (emulsifiable concentrate) in pre-emergence at a rate of 2.5 L ha-1) and fenoxaprop-p-ethyl (Puma Super 7.5 EW (emulsion in water) in post-emergence at a rate of 1.0 L ha-1), thanks to A. tenuifolius control, showed outstanding performance, providing the highest dietary quality of chickpea grain. The herbicides Stomp 330 EC, Buctril Super 40 EC, Starane-M 50 EC, and Puma Super 7.5 EW provided the highest levels of nitrogen. Outstanding increases in crude protein content were observed with all management strategies, particularly with Stomp 330 EC and Puma Super 7.5 EW (+18% on average). Ash content was highly elevated by Stomp 330 EC and Puma Super 7.5 EW, along with wheat straw mulching, reaching levels of 2.96% and 2.94%. Crude fat content experienced consistent elevations across all treatments, with the highest improvements achieved by Stomp 330 EC, Puma Super 7.5 EW, and wheat straw mulching applications. While 2018-19 displayed no significant oil content variations, 2019-20 revealed the highest oil content (5.97% and 5.96%) with herbicides Stomp 330 EC and Puma Super 7.5 EW, respectively, followed by eucalyptus leaves mulching (5.82%). The results here obtained are of key importance in the agricultural and food sector for the sustainable enhancement of chickpea grain's nutritional quality without impacting the environment.

Recent developments and challenges in uranium extraction from seawater through amidoxime-functionalized adsorbents.

As per statistical estimations, we have only around 100 years of uranium life in terrestrial ores. In contrast, seawater has viable uranium resources that can secure the future of energy. However, to achieve this, environmental challenges need to be overcome, such as low uranium concentration (3.3 ppb), fouling of adsorbents, uranium speciation, oceanic temperature, and competition between elements for the active site of adsorbent (such as vanadium which has a significant influence on uranium adsorption). Furthermore, the deployability of adsorbent under seawater conditions is a gigantic challenge; hence, leaching-resistant stable adsorbents with good reusability and high elution rates are extremely needed. Powdered (nanostructured) adsorbents available today have limitations in fulfilling these requirements. An increase in the grafting density of functional ligands keeping in view economic sustainability is also a major obstacle but a necessity for high uranium uptake. To cope with these challenges, researchers reported hundreds of adsorbents of different kinds, but amidoxime-based polymeric adsorbents have shown some remarkable advantages and are considered the benchmark in uranium extraction history; they have a high affinity for uranium because of electron donors in their structure, and their amphoteric nature is responsible for effective uranium chelation under a wide range of pH. In this review, we have mainly focused on recent developments in uranium extraction from seawater through amidoxime-based adsorbents, their comparative analysis, and problematic factors that are needed to be considered for future research.

An osteogenic, antibacterial, and anti-inflammatory nanocomposite hydrogel platform to accelerate bone reconstruction.

Fabricating an organic-inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague-Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues.

Exploring the therapeutic potential of Hibiscus rosa sinensis synthesized cobalt oxide (Co3O4-NPs) and magnesium oxide nanoparticles (MgO-NPs).

Herein, we present a green, economic and ecofriendly protocol for synthesis of cobalt oxide (Co3O4-NPs) and magnesium oxide nanoparticles (MgO-NPs) for multifaceted biomedical applications. In the study, a simple aqueous leaf extract of Hibiscus rosa sinensis, was employed for the facile one pot synthesis of Co3O4-NPs and MgO-NPs. The well characterized NPs were explored for multiple biomedical applications including bactericidal activity against urinary tract infection (UTI) isolates, leishmaniasis, larvicidal, antidiabetic antioxidant and biocompatibility studies. Our results showed that both the NPs were highly active against multidrug resistant UTI isolates as compared to traditional antibiotics and induced significant zone of inhibition against Proteus Vulgaris, Pseudomonas Aurigenosa and E.coli. The NPs, in particular Co3O4-NPs also showed significant larvicidal activity against the Aedes Aegypti, the mosquitoes involve in the transmission of Dengue fever. Similarly, excellent leishmanicidal activity was also observed against both the promastigote and amastigote forms of the parasite. Furthermore, the particles also exhibited considerable antidiabetic activity by inhibiting α-amylase and α-glucosidase enzymes. The biosynthesized NPs were found to be excellent antioxidant and biocompatible nanomaterials. Owing to ecofriendly synthesis, non-toxic and biocompatible nature, the Hibiscus rosa sinensis synthesized Co3O4-NPs and MgO-NPs can be exploited as potential candidates for multiple biomedical applications.

Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internalization and anticancer efficacy.

Despite enormous advancements in the field of oncology, the innocuous and effectual treatment of various types of malignancies remained a colossal challenge. The conventional modalities such as chemotherapy, radiotherapy, and surgery have been remained the most viable options for cancer treatment, but lacking of target-specificity, optimum safety and efficacy, and pharmacokinetic disparities are their impliable shortcomings. Though, in recent decades, numerous encroachments in the field of onco-targeted drug delivery have been adapted but several limitations (i.e., short plasma half-life, early clearance by reticuloendothelial system, immunogenicity, inadequate internalization and localization into the onco-tissues, chemoresistance, and deficient therapeutic efficacy) associated with these onco-targeted delivery systems limits their clinical viability. To abolish the aforementioned inadequacies, a promising approach has been emerged in which stealthing of synthetic nanocarriers has been attained by cloaking them into the natural cell membranes. These biomimetic nanomedicines not only retain characteristics features of the synthetic nanocarriers but also inherit the cell-membrane intrinsic functionalities. In this review, we have summarized preparation methods, mechanism of cloaking, and pharmaceutical and therapeutic superiority of cell-membrane camouflaged nanomedicines in improving the bio-imaging and immunotherapy against various types of malignancies. These pliable adaptations have revolutionized the current drug delivery strategies by optimizing the plasma circulation time, improving the permeation into the cancerous microenvironment, escaping the immune evasion and rapid clearance from the systemic circulation, minimizing the immunogenicity, and enabling the cell-cell communication via cell membrane markers of biomimetic nanomedicines. Moreover, the preeminence of cell-membrane cloaked nanomedicines in improving the bio-imaging and theranostic applications, alone or in combination with phototherapy or radiotherapy, have also been pondered.

Antidiabetic and Hypolipidemic Potential of Green AgNPs against Diabetic Mice.

Green nanotechnology-based approaches have been acquired as environmentally friendly and cost effective with many biomedical applications. The present study reports the synthesis of silver nanoparticles (AgNPs) from the leaves of Emblica phyllanthus, characterized by UV-Vis spectroscopy, EDX, SEM, AFM, and XRD. The acute and chronic antidiabetic and hypolipidemic potential of AgNPs was studied in alloxan-induced diabetic mice. A total of 11 groups (G1-G11, n = 6) of mice were treated with different concentrations (150 and 300 mM) and sizes of AgNPs and compared with those treated with standard glibenclamide. A significant decrease (P > 0.05) in the glucose level was achieved for 30, 45, and 65 nm after 15 days of treatment compared to the diabetic control. The oral administration of optimal AgNPs reduced the glucose level from 280.83 ± 4.17 to 151.17 ± 3.54 mg/dL, while the standard drug glibenclamide showed the reduction in glucose from 265.5 ± 1.43 to 192 ± 3.4 mg/dL. Histopathological studies were performed in dissected kidney and liver tissues of the treated mice, which revealed significant recovery in the liver and kidney after AgNP treatment. Acute toxicity study revealed that AgNPs were safe up to a size of 400 nm and the raw leaf extract of Emblica phyllanthus was safe up to 2500 mg/kg b.w. This study may help provide more effective and safe treatment options for diabetes compared to traditionally prescribed antidiabetic drugs.

Wheat growth and nutrient uptake after phosphorus and potassium applications in saline-sodic field of semi-arid region / Crescimento do trigo e absorção de nutrientes após aplicações de fósforo e potássio em campo salino-sódico do semi-árido

Nutrient deficiency is a limiting factor in saline-sodic soils resulting in low crop production. The study investigated wheat response to P and K added to soils. The K was applied at 0 (K0), 75 (K1), 150 (K2) kg K2O ha-1 as K2S04 and at (0 (P0), 60 (P1), 120 (P2) kg P2O5 ha-1 as (NH4)2HPO4 in three replications under two-factorial randomized complete block (RCB) design. Both treatments significantly enhanced wheat grain (118%) and dry matter yield (60%) at P2K2 compared to control. The P treatments significantly affected leaf P, Mg, SO4, Ca:P, SO4:P ratios and soil P, Ca:P, Cl:P and SO4:P ratios, while K on leaf K, Na, Ca, SO4 concentration, K:Na, K:Ca, SO4:P,Ca:P ratios and soil pH, Na, K, Ca, SO4 concentrations, SAR, Na:K, Ca:K and Na:Ca ratios. Leaf Na was decreased to 85.3 mmol (+) kg-1 at K2 compared to 105.3 mmol (+) kg-1at P2K0. Negative correlation (R2=0.906) of leaf K:Na was found with leaf Na concentration. The correlation of dry matter was higher (R2=0.851) with leaf K:Na ratio than grain yield (R2=0.392). It is concluded that the addition of K and P addition shows beneficial effects in improving crop nutrition and wheat yield in the saline-sodic soil environment.

A deficiência de nutrientes é um fator limitante em solos salino-sódicos, resultando em baixa produção agrícola. O estudo investigou a resposta do trigo ao P e K adicionados ao solo. O K foi aplicado em 0 (K0), 75 (K1), 150 (K2) kg K2O ha-1 como K2S04 e em (0 (P0), 60 (P1), 120 (P2) kg P2O5 ha-1 como (NH4)2HPO4 em três repetições sob delineamento de blocos completos casualizados (RCB) de dois fatores. Ambos os tratamentos aumentaram significativamente o rendimento de grãos de trigo (118%) e de matéria seca (60%) em P2K2 em comparação com o controle. Os tratamentos com P afetaram significativamente o P foliar, Mg, SO4, as razões Ca:P, SO4:P e o P do solo, e as razões Ca:P, Cl:P e SO4:P, enquanto K no K foliar, Na, Ca, concentração de SO4, razões K:Na, K:Ca, SO4:P, Ca:P e pH do solo, Na, K, Ca, concentrações de SO4, SAR, razões Na:K, Ca:K e Na:Ca. O Na da folha foi reduzido para 85,3 mmol (+) kg-1 em K2 em comparação com 105,3 mmol (+) kg-1 em P2K0. Correlação negativa (R2 = 0,906) do K:Na na folha foi encontrada com a concentração de Na na folha. A correlação da matéria seca foi maior (R2 = 0,851) com a relação K:Na da folha do que rendimento de grãos (R2 = 0,392). Conclui-se que a adição de K e P apresenta efeitos benéficos na melhoria da nutrição da cultura e na produtividade do trigo em solo salino-sódico

Therapeutic Role of Zinc Supplementation in Children Hospitalized with Pneumonia.

Introduction Pneumonia is one of the major causes of death in children younger than age five, especially in developing countries. The World Health Organization recommends children from a developing country take zinc supplements. We conducted this study to explore the efficacy of zinc supplementation in alleviating symptoms and shortening of hospital stay in children with pneumonia. Materials and methods We conducted this prospective, randomized controlled trial in the Department of Pediatrics, Civil Hospital, Jamshoro. We included 100 children of both genders randomized into two equal groups of zinc-supplemented and non-zinc-supplemented study groups after informed consent was obtained from the parents and legal guardians. The participants were aged 28 days to five years and admitted in the hospital with pneumonia. We monitored for hypoxia, tachypnea, chest indrawing, and cyanosis, and we recorded the total length of hospital stay for each group. Results We found no significant difference in symptom changes (i.e., hypoxia, tachypnea, chest indrawing, and cyanosis) between the zinc and non-zinc groups. However, hospital length of stay was significantly shorter for patients in the zinc-supplemented group compared to the non-zinc-supplemented group. Conclusion Zinc supplementation did not yield a statistically significant reduction in symptoms in children with severe pneumonia. Zinc supplements given during an acute episode are not beneficial in short-term clinical recovery from severe pneumonia in hospitalized children.

Novel biodegradable pH-sensitive hydrogels: An efficient controlled release system to manage ulcerative colitis.

The aim of this study was to develop and characterize a pH sensitive, biodegradable, interpenetrating polymeric network (IPNs) for colon specific delivery of sulfasalazine in ulcerative colitis. It also entailed in-vitro and in-vivo evaluations to optimize colon targeting efficiency, improve drug accumulation at the target site, and ameliorate the off-target effects of chemotherapy. Pectin was grafted with polyethylene glycol (PEG) and methacrylic acid (MAA) by free radical polymerization. Fourier transformed infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), energy dispersion X-ray (EDX) and powder X-ray diffraction (XRD) results confirmed the development of stable pectin-g-(PEG-co-MAA) hydrogels. The swelling and release studies exhibited that the hydrogels were capable of releasing drug specifically at colonic pH (pH 7.4). The toxicological potential of polymers, monomers and hydrogel was investigated using the Balb/c animal model, that confirmed the safety of the hydrogels. In vitro degradation of the hydrogel was evaluated using pectinase enzyme in various simulated fluids and the results showed that the hydrogels were susceptible to biodegradation by the natural microflora of the colon. In-vivo study was performed using Dextran sulphate sodium (DSS) rat model proved the hydrogels to be effective in the management of UC.

Effect of Zinc Supplementation on the Frequency and Consistency of Stool in Children with Acute Diarrhea.

Introduction Acute diarrhea in young children is a prevalent and distressing pediatric illness. The role of zinc therapy in the improvement of stool consistency and the shortening of the duration of diarrhea is still controversial. The aim of this study is to assess the effect of oral zinc supplementation in acute diarrhea. Methods Children of age 28 days till five years presenting in the outpatient department with acute diarrhea were included. Oral zinc supplementation was included in the anti-diarrheal regime of half of the children (n=50); the other half (n=50) were not given zinc. Mean body weight and the frequency and consistency of stool were noted for both groups on Days 1 and 3. Results The zinc group showed a significantly reduced frequency of diarrheal episodes on the third day of intervention (p<.00001). More children in the zinc group had soft to firm stool consistency than in the non-zinc group (p=.01). Conclusion Oral zinc supplementation has a promising role in reducing the duration of diarrhea and improving stool consistency in children with acute diarrhea. Oral zinc supplementation should be made a mandatory part of the anti-diarrheal regime for Pakistani children.

Synergistic effects of combined therapy of curcumin and Fructus Ligustri Lucidi for treatment of osteoporosis: cellular and molecular evidence of enhanced bone formation.

OBJECTIVE: The present study explored the effects of the combined herbal therapy consisting of curcumin (CUR) and Fructus Ligustri Lucidi (FLL) on aspects of bone regeneration. METHODS: Prior to analyzing the ability of this novel combined herbal therapy to promote aspects of bone regeneration, its cytotoxicity was determined using MC3T3-E1 cells (pre-osteoblast model). Cell proliferation was evaluated using phase-contrast microscopy and cell differentiation was estimated using alkaline phosphatase activity. The effect of the combined herbal therapy (CUR + FLL) was also assessed in terms of mineralization in the extracellular matrix (ECM) of cultured cells. Further, to explore the molecular mechanisms of bone formation, time-dependent expression of bone-regulating protein biomarkers was also evaluated. RESULTS: Combined herbal therapy (CUR + FLL) significantly upregulated the viability, proliferation and differentiation of MC3T3-E1 cells compared to the monotherapy of CUR or FLL. The magnitude of ECM mineralization (calcium deposition) was also higher in MC3T3-E1 cells treated with combined therapy. The time-dependent expression of bone-forming protein biomarkers revealed that the tendency of expression of these bone-regulating proteins was remarkably higher in cells treated with combined therapy. CONCLUSION: The co-administration of CUR and FLL had superior promotion of elements of bone regeneration in cultured cells, thus could be a promising alternative herbal therapy for the management of bone erosive disorders such as osteoporosis.

Eurycoma longifolia, a promising suppressor of RANKL-induced differentiation and activation of osteoclasts: An in vitro mechanistic evaluation.

BACKGROUND: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was not discovered yet. OBJECTIVES: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model. MATERIALS AND METHODS: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis. RESULTS: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures. CONCLUSION: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast's maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss.

Recent Advances in Antibacterial, Antiprotozoal and Antifungal Trends of Eurycoma longifolia: A Review of Therapeutic Implications and Future Prospects.

BACKGROUND: Eurycoma longifolia (E. longifolia) has gained widespread recognition due to its versatile pharmacological activities including aphrodisiac, anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti-diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti-ulcer effects. OBJECTIVE: This review was aimed to critically overview the literature and summarizes the antibacterial, antiprotozoal, and antifungal trends of E. longifolia and its medicinally active components. RESULTS: Besides its well-documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo, and human clinical studies has evidenced the antimicrobial efficacy of E. longifolia and its bioactive constituents. Phytochemical screening of various types of extracts (methanolic, ethyl acetate, and nbutanolic) from different parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent antibacterial, antiprotozoal, and antifungal responses. Comparative analysis revealed that the root extract of E. longifolia exhibited the highest antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided fractionation identified that among all of the medicinal compounds isolated/ extracted from different parts of E. longifolia, eurycomanone displayed the strongest antibacterial, antiprotozoal and antifungal activities. CONCLUSION: Based on the critical analysis of the literature, we identified that E. longifolia exhibits promising antibacterial, antiprotozoal, and antifungal efficacies against various pathogenic microbes and thus can be considered as a potential complementary and alternative antimicrobial therapy.

Phytomedicines are Efficient Complementary Therapies for the Treatment of Atopic Dermatitis: A Review of Mechanistic Insight and Recent Updates.

BACKGROUND: Phytomedicines have been well-accepted alternative complementary therapies for the treatment of a wide range of acute and chronic skin inflammatory diseases including chronic herpes, prurigo, psoriasis, and atopic dermatitis (AD). A plethora of in vitro and in vivo studies have evidenced the therapeutic viability of phytomedicines, polyherbal formulations, plant-based materials and their decoctions for the treatment of mild-to-severe AD. OBJECTIVE: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of phytomedicines for the treatment of AD and explore their anti-AD efficacy. RESULTS: The critical analysis of a wide algorithm of herbal medicines revealed that their remarkable anti-AD efficacy is attributed to their potential of reducing erythema intensity, oedema, inflammation, transepidermal water loss (TEWL) and a remarkable suppression of mRNA expression of ADassociated inflammatory biomarkers including histamine, immunoglobulin (Ig)-E, prostaglandins, mast cells infiltration and production of cytokines and chemokines in the serum and skin biopsies. CONCLUSION: In conclusion, herbal medicines hold great promise as complementary and alternative therapies for the treatment of mild-to-moderate AD when used as monotherapy and for the treatment of moderate-to-severe AD when used in conjunction with other pharmacological agents.

Eurycoma longifolia, A Potential Phytomedicine for the Treatment of Cancer: Evidence of p53-mediated Apoptosis in Cancerous Cells.

BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, antimalarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, antirheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent antiproliferative and anticancer efficacy against various types of human cancers. OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells. RESULTS: Among a range of medicinally active compounds isolated from various parts (roots, stem, bark and leaves) of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells). The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2). A remarkable alleviation in the mRNA expression of various cancer-associated biomarkers including heterogeneous nuclear ribonucleoprotein (hnRNP), prohibitin (PHB), annexin-1 (ANX1) and endoplasmic reticulum protein-28 (ERp28) has also been evidenced. CONCLUSION: Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.

Exploring molecular mechanism of bone-forming capacity of Eurycoma longifolia: Evidence of enhanced expression of bone-related biomarkers.

BACKGROUND: Among the numerous well-documented medicinal herbs, Eurycoma longifolia (EL) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Though numerous animal studies have explored the bone-forming capacity of EL, the exact mechanism was yet to be explored. OBJECTIVE(S): The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic model. MATERIALS AND METHODS: The cell differentiation capacity of EL was investigated by evaluating cell growth, alkaline phosphatase (ALP) activity, collagen deposition and mineralization. Taken together, time-mannered expression of bone-related mediators which include bone morphogenic protein-2 (BMP-2), ALP, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-ß1 (TGF-ß1) and androgen receptor (AR) were measured to comprehend bone-forming mechanism of EL. RESULTS: Results demonstrated a superior cell differentiation efficacy of EL (particularly at a dose of 25 µg/mL) that was evidenced by dramatically increased cell growth, higher ALP activity, collagen deposition and mineralization compared to the testosterone. Results analysis of the bone-related protein biomarkers indicated that the expression of these mediators was well-regulated in EL-treated cell cultures compared to the control groups. These findings revealed potential molecular mechanism of EL for the prevention and treatment of male osteoporosis. CONCLUSION: The resulting data suggested that EL exhibited superior efficacy in stimulating bone formation via up-regulating the expression of various mitogenic proteins and thus can be considered as a potential natural alternative therapy for the treatment of osteoporosis.

Emerging Trends in Therapeutic Algorithm of Chronic Wound Healers: Recent Advances in Drug Delivery Systems, Concepts-to-Clinical Application and Future Prospects.

Chronic wounds which include diabetic foot ulcer (DFU), pressure ulcer, and arterial or venous ulcers compel a significant burden to the patients, healthcare providers, and the healthcare system. Chronic wounds are characterized by an excessive persistent inflammatory phase, prolonged infection, and the failure of defense cells to respond to environmental stimuli. Unlike acute wounds, chronic nonhealing wounds pose a substantial challenge to conventional wound dressings, and the development of novel and advanced wound healing modalities is needed. Toward this end, numerous conventional wound-healing modalities have been evaluated in the management of nonhealing wounds, but a multifaceted approach is lacking. Therefore, this review aims to compile and explore the wide therapeutic algorithm of current and advanced wound healing approaches to the treatment of chronic wounds. The algorithm of chronic wound healing techniques includes conventional wound dressings; approaches based on autografts, allografts, and cultured epithelial autografts; and recent modalities based on natural, modified or synthetic polymers and biomaterials, processed mutually in the form of hydrogels, films, hydrocolloids, and foams. Moreover, this review also explores the promising potential of advanced drug delivery systems for the sustained delivery of growth factors, curcumin, aloe vera, hyaluronic acid, and other bioactive substances as well as stem cell therapy. The current review summarizes the convincing evidence for the clinical dominance of polymer-based chronic wound healing modalities as well as the latest and innovative therapeutic strategies for the treatment of chronic wounds.

Phytotherapeutic potential of natural herbal medicines for the treatment of mild-to-severe atopic dermatitis: A review of human clinical studies.

For many decades, natural herbal medicines, polyherbal formulations and/or decoctions of plant-derived materials have widely been accepted as alternative complementary therapies for the treatment, cure or prevention of a wide range of acute and chronic skin diseases including chronic herpes, prurigo, acute and chronic wounds, psoriasis and atopic dermatitis (AD). This review was aimed to summarize and critically discuss about the therapeutic viability and clinical applicability of natural herbal medicines for the treatment of AD in human. The critical analysis of the literature revealed that oral (in the form of capsules, syrup or granules) and/or topical application (alone or in conjunction with wet-wrap dressing and/or acupuncture) of natural herbal medicines exhibit remarkable potential for the treatment of mild-to-severe AD in adults, children, infants and in the pregnant women. In this review, the clinical efficacy of various herbal formulations such as Chinese herbal therapies, Korean medicines, Iranian medicines, honey, natural herbal oils (coconut oil, olive oil and mineral oil), beeswax, dodder seeds and whey for the treatment of AD has been discussed. The clinical anti-AD efficacy of these complementary therapies has been observed in terms of down-regulation in Scoring Atopic Dermatitis (SCORAD) index, erythematic intensity, Children's Dermatology Life Quality Index (CDLQI), Dermatology Life Quality Index (DLQI), pruritus and itching frequency, transepidermal water loss (TEWL) and expression of AD-mediated chemokines. Conclusively, we recognized that natural herbal medicines demonstrate remarkable clinical efficacy when used alone or in conjunction with other complementary therapies for the treatment of AD in patients of all ages as well as pregnant women.

Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies.

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.