Edible bird's nest (EBN) is recognized as a nourishing food among Chinese people. The efficacy of EBN was stated in the records of traditional Chinese medicine and its activities have been reported in many researches. Malaysia is the second largest exporter of EBNs in the world, after Indonesia. For many years, EBN trade to China was not regulated until August 2011, when a safety alert was triggered for the consumption of EBNs. China banned the import of EBNs from Malaysia and Indonesia due to high level of nitrite. Since then, the Malaysia government has formulated Malaysia Standards for swiftlet farming (MS 2273:2012), edible bird's nest processing plant design and management (MS 2333:2010), and edible bird's nest product quality (MS 2334:2011) to enable the industry to meet the specified standards for the export to China. On the other hand, Indonesia's EBN industry formulated a standard operating procedure (SOP) for exportation to China. Both countries can export EBNs to China by complying with the standards and SOPs. EBN contaminants may include but not limited to nitrite, heavy metals, excessive minerals, fungi, bacteria, and mites. The possible source of contaminants may come from the swiftlet farms and the swiftlets or introduced during processing, storage, and transportation of EBNs, or adulterants. Swiftlet house design and management, and EBN processing affect the bird's nest color. Degradation of its optical quality has an impact on the selling price, and color changes are tied together with nitrite level. In this review, the current and future prospects of EBNs in Malaysia and Indonesia in terms of their quality, and the research on the contaminants and their effects on EBN color changes are discussed.
Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties.Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone (1), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone (3), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified fromN. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds1,3, and4(12.5-25 mg/kg b.w.) exhibited dose-dependent and significant (p< 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound1,3, and4(12.5 mg/kg b.w.) demonstrated significant (p< 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAAreceptor in the action of compound3and4was evident from the reversal effects of flumazenil. In addition, compounds1and4(12.5-25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1-4) fromN. Plumbaginifoliacould be considered as suitable candidates for the development of analgesic and anxiolytic agents.
Aim: Due to their minimal side effects, the anti-cancer properties of the polyherbal formulation are being investigated. However, due to their low absorption potential, the administration of polyherbal formulations is restricted. Loading the polyherbal formulation into gold nanoparticles enhances the bioavailability of the polyherbal formulation (PHF) accompanied by reducing the concentration of doxorubicin (dox). Ferroptosis is one of the novel pathways that specifically target cancer stem cells due to high ferritin levels. Hence, in the present study, we conjugated polyherbal formulation with gold nanoparticles and studied its effect on inducing ferroptosis in drug-resistant breast cancer cell lines. Materials and methods: PHF and dox conjugated to gold nanoparticles were characterized using FTIR, UV-Vis spectrophotometer, DLS, particle size analyzer, and XRD. The drug entrapment and efficiency studies were performed to assess the biodegradable potential of the synthesized gold nanoparticles. Paclitaxel-resistant breast cancer stem cells were generated, and an MTT assay was performed to evaluate the cytotoxicity potential of AuNP-PHF and AuNP-dox. Scratch assay and clonogenic assay were performed to assess the migration and proliferation of the cells after treatment with chosen drug combinations. The ability of PHF and dox conjugated to gold nanoparticles to induce ferritinophagy was evaluated by RT-PCR. Finally, image analysis was performed to check apoptosis and cellular ROS using inverted fluorescent microscope. The ability to induce cell cycle arrest was assessed by cell cycle analysis using flow cytometer. Results and conclusion: PHF and dox conjugated to gold nanoparticles showed high stability and showed to induce ferritin degradation in drug resistant breast cancer stem cells through ferritin degradation. AuNP-PHF in combination with low dose of AuNP-Dox nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis.
A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy.
This study investigated the gastroprotective effect of Piper sarmentosum (PS) on stress-induced gastric ulcers in rats by measuring its effect on oxidative stress, gastric mucosal nitric oxide (NO), and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly divided into four groups; two control groups (non-stress and stress) and two treated groups supplemented with either methanolic PS extract (500 mg/kg body weight) or omeprazole (OMZ; 20 mg/kg) orally. After 28 days of treatment, the stress control, PS, and OMZ groups were subjected to water-immersion restrain stress (WIRS) for 3.5 h. Gastric tissue malondialdehyde (MDA), NO, superoxide dismutase (SOD), inducible NO synthase (iNOS), SOD mRNA, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. WIRS significantly increased gastric MDA, NO, and pro-inflammatory cytokine levels compared to the non-stressed control group. PS and omeprazole supplementation significantly reduced WIRS-exposure-induced gastric ulcers and MDA, iNOS, and IL-1β levels. However, only PS reduced NO, TNF-α, and IL-6 levels, which were upregulated in this ulcer model. In conclusion, the gastroprotection afforded by PS is possibly mediated by gastric mucosal NO normalization through reduced iNOS expression and attenuation of inflammatory cytokines. PS showed a greater protective effect than omeprazole in reducing gastric lesions and NO, TNF-α, and IL-6 levels, and iNOS expression.
Exposure to cigarette smoke is an important risk factor for cardiovascular diseases. Nicotine is an addictive compound in cigarette smoke that triggers oxidative stress, which leads to vascular dysfunction. Piper sarmentosum Roxb. is a herb with antioxidant and vascular protective effects. This study evaluated the potential protective effect of the aqueous extract of P. sarmentosum leaf (AEPS) on vascular dysfunction in rats induced with prolonged nicotine administration. A total of 22 male Sprague-Dawley rats were divided into control (normal saline, oral gavage [p.o.]), nicotine (0.8 mg/kg/day nicotine, intraperitoneally [i.p.]), and nicotine + AEPS groups (250 mg/kg/day AEPS, p.o. + 0.8 mg/kg/day nicotine, i.p.). Treatment was given for 21 days. Thoracic aortae were harvested from the rats for the measurement of vasorelaxation, vascular nitric oxide (NO) level, and antioxidant level and the assessment of vascular remodeling. Rats treated with AEPS had improved vasorelaxation to endothelium-dependent vasodilator, acetylcholine (ACh), compared with the nicotine-induced rats (p < 0.05). The presence of endothelium increased the maximum relaxation of aortic rings in response to ACh. Compared with the nicotine group, AEPS enhanced vascular NO level (p < 0.001) and increased antioxidant levels as measured by superoxide dismutase activity (p < 0.05), catalase activity (p < 0.01), and reduced glutathione level (p < 0.05). No remarkable changes in aortic histomorphometry were detected. In conclusion, P. sarmentosum attenuates vascular endothelial dysfunction in nicotine-induced rats by improving vasorelaxation and enhancing vascular NO and antioxidant levels.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS). ADMA is degraded by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of ADMA lead to reduction in nitric oxide (NO) production, which is linked to endothelial dysfunction and atherosclerosis. Piper sarmentosum is an herb that has shown stimulation on endothelial NO production by increasing both expression and activity of eNOS. Thus, this study determined whether the positive effect of P. sarmentosum on NO production is related to its modulation on the DDAH-ADMA pathway in cultured human umbilical vein endothelial cells (HUVEC) exposed to tumor necrosis factor-α (TNF-α). HUVEC were divided into four groups: control, treatment with 250 µg/ml of aqueous extract of P. sarmentosum leaves (AEPS), treatment with 30 ng/ml of TNF-α, and concomitant treatment with AEPS and TNF-α for 24 h. After treatments, HUVEC were collected to measure DDAH1 messenger RNA (mRNA) expression using quantitative real-time polymerase chain reaction. DDAH1 protein level was measured using enzyme-linked immunosorbent assay (ELISA), and DDAH enzyme activity was measured using colorimetric assay. ADMA concentration was measured using ELISA, and NO level was measured using Griess assay. Compared to control, TNF-α-treated HUVEC showed reduction in DDAH1 mRNA expression (P < 0.05), DDAH1 protein level (P < 0.01), and DDAH activity (P < 0.05). Treatment with AEPS successfully increased DDAH1 mRNA expression (P < 0.05), DDAH1 protein level (P < 0.01), and DDAH activity (P < 0.05) in TNF-α-treated HUVEC. Treatment with TNF-α caused an increase in ADMA level (P < 0.01) and a decrease in endothelial NO production (P < 0.001). Whereas treatment with AEPS was able to reduce ADMA level (P < 0.01) and restore NO (P < 0.001) in TNF-α-treated HUVEC. The results suggested that AEPS promotes endothelial NO production by stimulating DDAH activity and thus reducing ADMA level in TNF-α-treated HUVEC.
Sphaeranthus indicus L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and in vitro reactivity of six different polarity solvents (methanol, n-hexane, benzene, chloroform, ethyl acetate, and n-butanol) extracts/fractions of S. indicus flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, α-glucosidase, α-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07 mg GAE/g extract) and flavonoid (78.7 mg QE/g extract) contents and was also the most active for α-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the n-hexane fraction was most active for α-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, S. indicus flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.
This study assessed the toxicity of lutein-rich purple sweet potato leaf (PSPL) extract in male Sprague-Dawley rats. Methods and study design: A total of 54 adult male Sprague-Dawley rats were used. For the acute toxicity study, three rats in the acute control group were fed 2,000 mg/kg of PSPL for 14 days. The subacute toxicity study included six rats each in four groups administered 50, 250, 500, or 1,000 mg/kg for 28 days and observed for further 14 days without treatment in the subacute control and subacute satellite groups. Changes in body weight; blood biochemistry; hematological parameters; relative organ weight; and histological sections of the heart, kidney, liver, pancreas, aorta, and retina were observed for signs of toxicity. Results: The gradual increase in weekly body weight, normal level full blood count, normal liver and kidney profile, relative organ weight, and histological sections of all stained organ tissue in the treated group compared with the acute, subacute, and satellite control groups demonstrated the absence of signs of toxicity. Conclusion: Lutein-rich PSPL extract shows no signs of toxicity up to 2,000 mg/kg/day.
Blainvillea acmella (L.) Philipson [Asteraceae] (B. acmella) is an important medicinal plant native to Brazil, and it is widely known as a toothache plant. A plethora of studies have demonstrated the antioxidant activities of B. acmella and few studies on the stimulatory effects on alkaline phosphatase (ALP) secretion from bone cells; however, there is no study on its antioxidant and anabolic activity on bone cells. The study aimed to evaluate the phytochemical contents of aqueous and ethanol extracts of B. acmella using gas chromatography mass spectrometry (GCMS) and liquid chromatography time of flight mass spectrometry (LCTOFMS) along with the total phenolic (TPC) and flavonoid (TFC) contents using Folin-Ciocalteu and aluminum colorimetric methods. The extracts of B. acmella leaves were used to scavenge synthetic-free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. The bone anabolic effects of B. acmella extracts on MC3T3-E1 cells were measured with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoium bromide (MTT) at 1, 3, 5, and 7 days, Sirius-red and ALP at 7 and 14 days, and Alizarin Red S at 14 and 21 days. Comparatively, ethanol extract of B. acmella (BaE) contributed higher antioxidant activities (IC50 of 476.71 µg/ml and 56.01 ± 6.46 mg L-ascorbic acid/g against DPPH and FRAP, respectively). Anabolic activities in bone proliferation, differentiation, and mineralization were also higher in B. acmella of ethanol (BaE) than aqueous (BaA) extracts. Positive correlations were observed between phenolic content (TPC and TFC) to antioxidant (ABTS and FRAP) and anabolic activities. Conversely, negative correlations were present between phenolic content to antioxidant (DPPH) activity. These potential antioxidant and bone anabolic activities in BaE might be due to the phytochemicals confirmed through GCMS and LCTOFMS, revealed that terpenoids of α-cubebene, cryophyllene, cryophyllene oxide, phytol and flavonoids of pinostrobin and apigenin were the compounds contributing to both antioxidant and anabolic effects in BaE. Thus, B. acmella may be a valuable antioxidant and anti-osteoporosis agent. Further study is needed to isolate, characterize and elucidate the underlying mechanisms responsible for the antioxidant and bone anabolic effects.
Phyllanthus emblica Linn, a prominent member of the euphorbiaceae family, exhibits extensive distribution across a multitude of tropical and subtropical nations. Referred to as "Balakka" in Indonesia, this plant assumes various names across regions, such as "kimalaka," "balakka," "metengo," "malaka," and "kemloko" in North Sumatra, Ternate, Sundanese, and Java respectively. Phyllanthus emblica thrives in tropical locales like Indonesia, Malaysia, and Thailand, while also making its presence felt in subtropical regions like India, China, Uzbekistan, and Sri Lanka. The fruits of Balakka are enriched with bioactive constituents recognized for their wide-ranging benefits, including antioxidant, anti-aging, anti-cholesterol, anti-diabetic, immunomodulatory, antipyretic, analgesic, anti-inflammatory, chemoprotective, hepatoprotective, cardioprotective, antimutagenic, and antimicrobial properties. Comprising a spectrum of phenolic compounds (such as tannins, phenolic acids, and flavonoids), alkaloids, phytosterols, terpenoids, organic acids, amino acids, and vitamins, the bioactive components of Malacca fruit offer a diverse array of health-promoting attributes. In light of these insights, this review aims to comprehensively examine the pharmacological activities associated with P. emblica and delve into the intricate composition of its phytochemical constituents.
Alzheimer's disease (AD) is recognized as a major health hazard that mostly affects people older than 60 years. AD is one of the biggest medical, economic, and social concerns to patients and their caregivers. AD was ranked as the 5th leading cause of global deaths in 2016 by the World Health Organization (WHO). Many drugs targeting the production, aggregation, and clearance of Aβ plaques failed to give any conclusive clinical outcomes. This mainly stems from the fact that AD is not a disease attributed to a single-gene mutation. Two hallmarks of AD, Aβ plaques and neurofibrillary tangles (NFTs), can simultaneously induce other AD etiologies where every pathway is a loop of consequential events. Therefore, the focus of recent AD research has shifted to exploring other etiologies, such as neuroinflammation and central hyperexcitability. Neuroinflammation results from the hyperactivation of microglia and astrocytes that release pro-inflammatory cytokines due to the neurological insults caused by Aβ plaques and NFTs, eventually leading to synaptic dysfunction and neuronal death. This review will report the failures and side effects of many anti-Aβ drugs. In addition, emerging treatments targeting neuroinflammation in AD, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and receptor-interacting serine/threonine protein kinase 1 (RIPK1), that restore calcium dyshomeostasis and microglia physiological function in clearing Aβ plaques, respectively, will be deliberately discussed. Other novel pharmacotherapy strategies in treating AD, including disease-modifying agents (DMTs), repurposing of medications used to treat non-AD illnesses, and multi target-directed ligands (MTDLs) are also reviewed. These approaches open new doors to the development of AD therapy, especially combination therapy that can cater for several targets simultaneously, hence effectively slowing or stopping AD.
Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.
Hypophyllanthin is a major lignan present in various Phyllanthus species and has been used as one of the bioactive chemical markers for quality control purposes as it contributes to their diverse pharmacological activities. The objective of this study is to compile up-to-date data on the pharmacological actions and mechanisms of hypophyllanthin. This review also includes the extracts of Phyllanthus species whose pharmacological actions have been partially attributed to hypophyllanthin. The scientific findings on the compound are critically analyzed and its potential as a lead molecule for the discovery of drug candidates for the development of therapeutics to treat diverse diseases is highlighted. Data collection was mainly through the exploration of Ovid-MEDLINE, Scopus, Science Direct, and Elsevier databases. Studies conducted in vitro and in vivo showed that hypophyllanthin had potent immunomodulating properties as well as a variety of other pharmacological properties, including anti-inflammatory, hepatoprotective, anti-tumor, anti-allergic, anti-hypertensive, and phytoestrogenic properties. Several mechanisms of action on the effects of hypophyllanthin on the immune system, in cancer and other disease states, were presented to provide some insights into its pharmacological effects. Before being submitted to clinical investigations, additional animal studies utilising different animal models are necessary to analyse its bioavailability, pharmacokinetics, and pharmacodynamic properties, as well as its toxicity, to determine its efficacy and safety. Understanding its potential as a lead molecule for the discovery of therapeutic candidates, particularly for the development of therapies for inflammatory and immune-related disorders, requires an understanding of its pharmacological activities and mechanisms of action. An insight into its pharmacological activities and mechanisms of action will provide an understanding of its potential as a lead compound for the discovery of drug candidates, especially for the development of therapies for inflammatory and immune related diseases.
2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a bioactive phloroglucinol compound found in Melicope pteleifolia (Champ. ex Benth.) T.G.Hartley, a medicinal plant vernacularly known as "tenggek burung". A variety of phytochemicals have been isolated from different parts of the plant including leaves, stems, and roots by using several extraction methods. Specifically, tHGA, a drug-like compound containing phloroglucinol structural core with acyl and geranyl group, has been identified in the methanolic extract of the young leaves. Due to its high nutritional and medicinal values, tHGA has been extensively studied by using various experimental models. These studies have successfully discovered various interesting pharmacological activities of tHGA such as anti-inflammatory, endothelial and epithelial barrier protective, anti-asthmatic, anti-allergic, and anti-cancer. More in-depth investigations later found that these activities were attributable to the modulatory actions exerted by tHGA on specific molecular targets. Despite these findings, the association between the mechanisms and signaling pathways underlying each pharmacological activity remains largely unknown. Also, little is known about the medicinal potentials of tHGA as a drug lead in the current pharmaceutical industry. Therefore, this mini review aims to summarize and relate the pharmacological activities of tHGA in terms of their respective mechanisms of action and signaling pathways in order to present a perspective into the overall modulatory actions exerted by tHGA. Besides that, this mini review will also pinpoint the unexplored potentials of this compound and provide some valuable insights into the potential applications of tHGA which may serve as a guide for the development of modern medication in the future.
Safoof-e-Pathar phori (SPP) is an Unani poly-herbomineral formulation, which has for a long time been used as a medicine due to its antiurolithiatic activity, as per the Unani Pharmacopoeia. This powder formulation is prepared using six different plant/mineral constituents. In this study, we explored the antiurolithiatic and antioxidant potentials of SPP (at 700 and 1,000 mg/kg) in albino Wistar rats with urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC). Long-term oral toxicity studies were performed according to the Organization for Economic Co-operation and Development (OECD) guidelines for 90 days at an oral dose of 700 mg/kg of SPP. The EG urolithiatic toxicant group had significantly higher levels of urinary calcium, serum creatinine, blood urea, and tissue lipid peroxidation and significantly (p < 0.001 vs control) lower levels of urinary sodium and potassium than the normal control group. Histopathological examination revealed the presence of refractile crystals in the tubular epithelial cell and damage to proximal tubular epithelium in the toxicant group but not in the SPP treatment groups. Treatment of SPP at 700 and 1,000 mg/kg significantly (p < 0.001 vs toxicant) lowered urinary calcium, serum creatinine, blood urea, and lipid peroxidation in urolithiatic rats, 21 days after induction of urolithiasis compared to the toxicant group. A long-term oral toxicity study revealed the normal growth of animals without any significant change in hematological, hepatic, and renal parameters; there was no evidence of abnormal histology of the heart, kidney, liver, spleen, or stomach tissues. These results suggest the usefulness of SPP as an antiurolithiatic and an antioxidant agent, and long-term daily oral consumption of SPP was found to be safe in albino Wistar rats for up to 3 months. Thus, SPP may be safe for clinical use as an antiurolithiatic formulation.
Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years. However, the side effects of systemic therapy such as toxicity may cause fatal complications and have a major consequences on the patients' quality of life. Hence, there is an urgent need for key biomarkers which will enable the selection of optimal drug singly or in combination for an individual patient. The application of personalized therapy based on DNA testing could aid the clinicians in providing the most effective chemotherapy agents and dose modifications for each patient. Yet, some of the current findings are controversial and the evidences are conflicting. This review aims at summarizing the current state of knowledge about germline pharmacogenomics DNA variants that are currently used to guide therapeutic decisions and variants that have the potential to be clinically useful in the future. In addition, current updates on germline variants conferring treatment sensitivity, drug resistance to existing chemotherapy agents and variants affecting prognosis and survival will also be emphasized. Different alteration in the same gene might confer resistance or enhanced sensitivity; and while most of other published reviews generally stated only the gene name and codon location, we will specifically discuss the exact variants to offer more accurate information in this mini review.
Background: Optimal collaboration between pharmacists and other healthcare professionals such as physicians is integral in implementing pharmaceutical care. However, there are concerns regarding the role of pharmacists, especially among low- and middle-income countries. This study explored the perceptions, expectations, and experience of physicians working in various hospital settings of Punjab, Pakistan, about pharmacists and their roles. Methods: A self-administered questionnaire consisting of four sections was administered from October to December 2020. Descriptive and inferential statistics such as Kruskal-Wallis and Mann-Whitney tests were used for data analysis using SPSS. Results: Six hundred and seventy-eight physicians participated in this study with a response rate of 77.9%. Most of the physicians reported minimal to no interaction with pharmacists (n = 521, 76.8%). However, more than three-quarters of physicians (n = 660, 97.3%) accepted pharmacists as evidence-based sources of drug information. In addition, many physicians (n = 574, 84.7%) strongly agreed that pharmacists should attend patient care rounds to respond promptly to questions related to patient medication. A limited number of physicians (n = 124, 18.3%) assumed that pharmacists were advising their patients regarding the judicial use of their drugs. Median expectation and experience score had a significant association with age, experience, and education of physicians (P < 0.05). Conclusions: The perception of physicians was positive toward certain roles of pharmacists, coupled with high expectations. However, their experience was low, with most of the activities of pharmacists due to inadequate interprofessional coordination.
Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.
Osteoporosis and periodontitis are two major chronic diseases of postmenopausal women. The association between these two diseases are evident through systemic bone loss and alveolar bone loss. Both postmenopausal osteoporosis and periodontitis impose a considerable personal and socioeconomic burden. Biphosphonate and hormone replacement therapy are effective in preventing bone loss in postmenopausal osteoporosis and periodontitis, but they are coupled with severe adverse effects. Phytoestrogens are plant-based estrogen-like compounds, which have been used for the treatment of menopause-related symptoms. In the last decades, numerous preclinical and clinical studies have been carried out to evaluate the therapeutic effects of phytoestrogens including bone health. The aim of this article is to give an overview of the bidirectional interrelationship between postmenopausal osteoporosis and periodontitis, summarize the skeletal effects of phytoestrogens and report the most studied phytoestrogens with promising alveolar bone protective effect in postmenopausal osteoporosis model, with and without experimental periodontitis. To date, there are limited studies on the effects of phytoestrogens on alveolar bone in postmenopausal osteoporosis. Phytoestrogens may have exerted their bone protective effect by inhibiting bone resorption and enhancing bone formation. With the reported findings on the protective effects of phytoestrogens on bone, well-designed trials are needed to better investigate their therapeutic effects. The compilation of outcomes presented in this review may provide an overview of the recent research findings in this field and direct further in vivo and clinical studies in the future.