Tentatively Identified (UPLC/T-TOF–MS/MS) Compounds in the Extract of Saussurea costus Roots Exhibit In Vivo Hepatoprotection via Modulation of HNF-1α, Sirtuin-1, C/ebpα, miRNA-34a and miRNA-223

Saussurea costus is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF–MS/MS analysis of a methanol extract of Saussurea costus roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that Saussurea costus may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223

Enhancement of Antimicrobial and Antiproliferative Activities of Standardized Frankincense Extract Using Optimized Self-Nanoemulsifying Delivery System

Boswellic acids (BAs) are the main bioactive compounds of frankincense, a natural resin obtained from the genus Boswellia. This study aimed to develop a self-nanoemulsifying delivery system (SNEDS) to improve the antimicrobial and antiproliferative activities of standardized frankincense extract (Fr-extract). Fr-extract was standardized, and BA content was quantified using the developed HPLC-UV method. Screening studies of excipients followed by formula optimization using a mixture simplex lattice design was employed. The optimized Fr-SENDS formulation was characterized. Furthermore, microbiological and antiproliferative assessments of the standardized Fr-extract and Fr-SNEDS were evaluated. Quantification demonstrated that the major constituent is 11-keto-boswellic acid (KBA) (16.25%) among BA content (44.96%). The optimized Fr-SENDS (composed of 5% CapryolTM 90, 48.7% Gelucire® 44/14 and 46.3% ethanol) showed spherical nanosized dispersions with DS, PDI, and zeta potential of 17.9 nm, 0.2, and −14.5 mV, respectively. Fr-SNEDS exhibited lower MIC and MBC values compared with Fr-extract against pathogens conjugated with lung cancer and was comparable to reference antimicrobials. Fr-SNEDS showed superior antiproliferative activity over Fr-extract, with IC50 values of 20.49 and 109.5 μg mL−1, respectively. In conclusion, the optimized Fr-SNEDS could be easily developed and manufactured at a low cost and the in vitro results support its use as a potential adjuvant oral therapy for lung cancer. Further in vivo studies could be continued to assess the therapeutic efficiency of the prepared system

Aldose reductase inhibitor form Cassia glauca: A comparative study of cytotoxic activity with Ag nanoparticles (NPs) and molecular docking evaluation.

UPLC-MS/MS profiling of Cassia glauca leaves extract revealed the identification of 10 flavonoids. Kaempferol 3-O-β-D-rutinoside was isolated and studied for its cytotoxic activity. It showed high cytotoxic effects against MCF-7 (IC50 of 4.6±0.038 μg/ml) and HepG-2 (IC50 of 8.2±0.024 μg/ml) cancer cell lines, compared to the leaves extracts, their Ag nanoparticles, and doxorubicin. Moreover, Kaempferol 3-O-β-D-rutinoside exerted a synergistic cytotoxic effect with doxorubicin on MCF-7 cell lines. It was discovered as kinases and aldose reductase inhibitor while rationalizing its cytotoxic activity through molecular docking study. Thus, it is expected that the cardiotoxic effects of doxorubicin can be also decreased by using Kaempferol 3-O-β-D-rutinoside due to its aldose reductase inhibitory effect. These findings suggested that Kaempferol 3-O-β-D-rutinoside could be used in combination with chemotherapeutic drugs to increase the sensitivity to their cytotoxic activity and protect against their side effects

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially