In this contribution, we provide a comprehensive overview of acyclic twisted amides, covering the literature since 1993 (the year of the first recognized report on acyclic twisted amides) through June 2020. The review focuses on classes of acyclic twisted amides and their key structural properties, such as amide bond twist and nitrogen pyramidalization, which are primarily responsible for disrupting nN to π*C═O conjugation. Through discussing acyclic twisted amides in comparison with the classic bridged lactams and conformationally restricted cyclic fused amides, the reader is provided with an overview of amidic distortion that results in novel conformational features of acyclic amides that can be exploited in various fields of chemistry ranging from organic synthesis and polymers to biochemistry and structural chemistry and the current position of acyclic twisted amides in modern chemistry.

Acyclic Twisted Amides.

Oviductus ranae is an animal-based traditional Chinese material widely used as tonics in China for hundreds of years. Various bioactive components are present in OR including proteins, amino acids, steroids, fatty acids, phospholipids, nucleosides, vitamins, hydantoins, and mineral elements. These constituents exert a myriad of biological functions such as immunomodulatory, antioxidant, antifatigue, antiaging, estrogen-like, hepatoprotective, hypolipidemic, antiosteoporotic, antidepressant, antitumor, antitussive, expectorant, anti-inflammatory, and antiasthmatic activities. Unlike other traditional Chinese crude drugs recorded in Chinese Pharmacopoeia, OR is seldom prescribed as medicine but often consumed as nutraceuticals to optimize health. In this review, the traditional uses, bioactive constituents, biological functions, and safety properties of OR as functional foods in China were summarized and discussed. It is expected that this review will provide useful information for anyone who is interested in OR.

/pdf/traditional-uses-bioactive-constituents-biological-functions-1ud0p8sj5o.pdf

Traditional Uses, Bioactive Constituents, Biological Functions, and Safety Properties of Oviductus ranae as Functional Foods in China.

In order to achieve the comprehensive quality control of Chinese herbal medicine (CHM), the conventional practice of selecting a single marker for testing has been gradually replaced by the determination of multiple active components based on the characteristics of the synergistic interaction of CHM and applicability of sophisticated analytical techniques. However, with a huge number of CHM in the market and more complex preparations, the limited availability of various standard substances for quantitative analysis has been a major bottleneck in realizing the goal. To overcome these uprising problems, quantitative analysis of multi-components by single marker (QAMS) was proposed and accepted as a new method to reflect the internal quality of CHM. In this review, the current knowledge about QAMS is systematically summarized, including the general content of QAMS, current status, and general procedure. Additionally, speculation is proposed about the future applications of QAMS approaches in the modernization and standardization of CHM.

Quantitative analysis of multi-components by single marker—a rational method for the internal quality of Chinese herbal medicine

Epidemiologists have been studying the effect of n-6 polyunsaturated fatty acids (PUFAs) intake on the risk of cardiovascular disease (CVD) for many decades. Abundant evidence from prospective studies on the clinical endpoints of CVD, including cohort studies measuring n-6 PUFA intake by food frequency questionnaires and nested case-control studies using biomarkers of intake level, strongly support that higher intakes of n-6 PUFAs are associated with a lower risk of CVD. Furthermore, a significant reduction in CVD risk can be achieved when saturated fatty acids (SFAs) is replaced by n-6 PUFAs. Evidence from appropriately designed and vigorously executed randomized controlled trials support that high-PUFA (predominantly linoleic acid) and low-SFA diets, compared to high-SFA diets, reduced the risk of coronary heart disease. Overall, epidemiologic studies provide a solid evidence base of the current dietary guidelines that recommend replacing SFA by PUFA, both n-6 and n-3 PUFA, for CVD prevention.

Dietary n-6 polyunsaturated fatty acids and cardiovascular disease: Epidemiologic evidence.

Cyclooxygenases (COXs) are the key enzymes in the biosynthesis of prostanoids. COX-1 is a constitutive enzyme while the expression of COX-2 is highly stimulated in the event of inflammatory processes, leading to the production of large amounts of prostaglandins (PGs), in particular PGE(2) and PGI(2), which are pro-inflammatory mediators. Lipoxygenases (LOXs) are enzymes that produce hydroxy acids and leukotrienes (LTs). 5-LOX metabolizes arachidonic acid to yield, among other products, LTB(4), a potent chemoattractant mediator of inflammation. The aim of the present work was to evaluate the anti-inflammatory potential of 2-styrylchromones (2-SC), a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), by studying their COX-1 and COX-2 inhibitory capacity as well as their effects on the LTB(4) production by stimulated human polymorphonuclear leukocytes (PMNL). Some of the tested 2-SC were able to inhibit both COX-1 activity and LTB(4) production which makes them dual inhibitors of the COX and 5-LOX pathways. The most effective compounds in this study were those having structural moieties with proved antioxidant activity (3',4'-catechol and 4'-phenol substituted B-rings). This type of compounds may exhibit anti-inflammatory activity with a wider spectrum than that of classical non-steroidal anti-inflammatory drugs (NSAIDs) by inhibiting 5-LOX product-mediated inflammatory reactions, towards which NSAIDs are ineffective.

/pdf/anti-inflammatory-potencial-of-2-styrylchromones-regarding-1llr6gwxki.pdf

Anti-inflammatory potencial of 2-Styrylchromones regarding their interference with arachidonic acid metabolic pathways

A method, quantitative analysis of multicomponents by single marker (QAMS), was established in this article to investigate the quality control of a traditional Chinese medicine, Oviductus Ranae. 7-Hydroxycholesterol, 7-ketocholesterol, 4-cholesten-3-one, stigmasterol, 7-dehydrocholesterol, and cholesterol were selected as the indexes of quality evaluation of Oviductus Rana. The determination was achieved on an Agilent HC-C18 column (4.6 mm × 250 mm, 5 μm) using methanol with water (87 : 13 v/v) as mobile phase at the flow rate of 2.0 mL/min. Cholesterol was used as an internal standard to determine the relative correction factors between cholesterol and other steroidal constituents in Oviductus Ranae. The contents of those steroidal constituents were calculated at the same time. To evaluate the QAMS method, an external standard method was used to determine the contents of six steroidal constituents. No significant difference was observed when comparing the quantitative results of QAMS with the results of external standard method. The proposed QAMS method was proved to be accurate and feasible based on methodological experiments. QAMS provided a simple, efficient, economical, and accurate way to control the quality of Oviductus Ranae.

/pdf/simultaneous-determination-of-six-active-components-in-41g91928p3.pdf

Simultaneous Determination of Six Active Components in Oviductus Ranae via Quantitative Analysis of Multicomponents by Single Marker

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.

Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.

Oviductus Ranae is a nutritional product for both medicine and food. Its quality is uneven due to multiple factors. An efficient method was established to evaluate the quality of Oviductus Ranae using fingerprint techniques and chemometric methods based on the analysis of polyunsaturated fatty acids (PUFAs) in petroleum ether extract by high performance liquid chromatography (HPLC). During this process, 27 batches of Oviductus Ranae were analyzed by HPLC and two types of chromatographic fingerprints were established. The fingerprint that was obtained by matching six known peaks was used for the quantification of six PUFAs. Another fingerprint was obtained by matching sixteen peaks with a peak area ratio greater than 0.5% and it was used to classify the different qualities of Oviductus Ranae by further combining three different chemometric models. The 27 batches of Oviductus Ranae were divided into four categories, which was consistent with the analysis results of six PUFAs contents. The two high-quality samples with significantly higher contents were classified into one category, and samples with medium contents were divided into two categories, including eight and thirteen samples, respectively. The four inferior samples with lower contents were classified into one category. The results indicated that the newly developed method has potential application prospects for the quality evaluation of Oviductus Ranae.

Quality Evaluation of Oviductus Ranae Based on PUFAs Using HPLC Fingerprint Techniques Combined with Chemometric Methods

Rana chensinensis ovum oil (RCOO) is an emerging source of unsaturated fatty acids (UFAs), but it is lacking in green and efficient extraction methods. In this work, using the response surface strategy, we developed a green and efficient CO2 supercritical fluid extraction (CO2-SFE) technology for RCOO. The response surface methodology (RSM), based on the Box-Behnken Design (BBD), was used to investigate the influence of four independent factors (pressure, flow, temperature, and time) on the yield of RCOO in the CO2-SFE process, and UPLC-ESI-Q-TOP-MS and HPLC were used to identify and analyze the principal UFA components of RCOO. According to the BBD response surface model, the optimal CO2-SFE condition of RCOO was pressure 29 MPa, flow 82 L/h, temperature 50 °C, and time 132 min, and the corresponding predicted optimal yield was 13.61%. The actual optimal yield obtained from the model verification was 13.29 ± 0.37%, and the average error with the predicted value was 0.38 ± 0.27%. The six principal UFAs identified in RCOO included eicosapentaenoic acid (EPA), α-linolenic acid (ALA), docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (LA), and oleic acid (OA), which were important biologically active ingredients in RCOO. Pearson correlation analysis showed that the yield of these UFAs was closely related to the yield of RCOO (the correlation coefficients were greater than 0.9). Therefore, under optimal conditions, the yield of RCOO and principal UFAs always reached the optimal value at the same time. Based on the above results, this work realized the optimization of CO2-SFE green extraction process and the confirmation of principal bioactive ingredients of the extract, which laid a foundation for the green production of RCOO.

https://www.mdpi.com/1420-3049/25/18/4170/pdf

Rana chensinensis Ovum Oil Based on CO2 Supercritical Fluid Extraction: Response Surface Methodology Optimization and Unsaturated Fatty Acid Ingredient Analysis.

To ensure the highest quality of Oviductus Ranae products for consumers, an accurate, efficient, scientific and comprehensive evaluation method for assessing the quality of Oviductus Ranae was proposed in this paper. The fingerprint of Oviductus Ranae has been established based on the method of high performance liquid chromatography (HPLC). Oviductus Ranae from different habitats were analyzed by hierarchical cluster analysis (HCA). The HPLC profiles of fourteen batches of Oviductus Ranae showed 33 well-resolved common peaks in each chromatogram. Five of these were assigned to 1-methyl hydantoin, 7-ketocholesterol, 4-cholesten-3-one, cholesterol and stigmasterol. Contents of these five main effective components were determined in the meantime. Based on the HPLC profiles of all the samples, the reference HPLC fingerprint and similarity values were calculated by statistical software (SPSS 19.0). It was found that similarity value of all Oviductus Ranae samples were more than 0.85 and Oviductus Ranae from same habitats had similarity to some degree. In conclusion, the proposed method had good specificity, repeatability, stability and precision, which can provide a reference for the quality evaluation and identification of the medicine origin of Oviductus Ranae. Quantitation of effective components revealed that contents of five effective constituents in Oviductus Ranae obtained from Ji Lin province were the highest, followed by Hei Longjiang province and Liaoning province. The results of HCA showed that samples classified into one group were associated with their habitats. HPLC fingerprint combined with quantitation of main effective compounds and data analysis techniques can be an efficient and useful method for monitoring the quality of Oviductus Ranae.

https://journals.sagepub.com/doi/pdf/10.1177/1934578X1701200929

HPLC Fingerprint Combined with Quantitation of Main Effective Components and Chemometrics as an Efficient Method for Quality Evaluation of Oviductus Ranae

Yongsheng Wang

Papers

Simultaneous Determination of Six Active Components in Oviductus Ranae via Quantitative Analysis of Multicomponents by Single Marker

Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.

Quality Evaluation of Oviductus Ranae Based on PUFAs Using HPLC Fingerprint Techniques Combined with Chemometric Methods

Rana chensinensis Ovum Oil Based on CO2 Supercritical Fluid Extraction: Response Surface Methodology Optimization and Unsaturated Fatty Acid Ingredient Analysis.

HPLC Fingerprint Combined with Quantitation of Main Effective Components and Chemometrics as an Efficient Method for Quality Evaluation of Oviductus Ranae