A review on ethno-medicinal plants used in traditional medicine in the Kingdom of Saudi Arabia

The traditional medicine based on medicinal plants in the Kingdom of Arabia Saudia presents a strong relationship belonging to natural remedies, health, diet, and folk healing practice recognized by a specific culture. The aim of the current study is to carry out an ethnobotanical review on medicinal plants used in traditional medicine in the Kingdom of Arabia Saudia including information on plant species, used parts, preparation method as well as medical uses. Earlier published data in journals, textbooks, periodicals, websites, and databases written in pharmacological evidence of Suadi medicinal plants were based on gathering information. The present review work reported that 96 species belonging to 47 families have been used in Saudi Pharmacopeia. Amaranthaceae has the highest number of plant species (7) Followed by Asteraceae, Apocynaceae, and Fabaceae with 5 plant species in each. The inventoried plant species in the current work are frequently used for the treatment of various illnesses and to ensure the medication safety of Saudi people. The biological analysis of plant form used in Saudi natural remedies showed the dominance of herb and subshrub form with a percentage of 43% and 30% respectively. The most used preparation method of plant drugs, which used in Saudi Alternative medicine was decoction and infusion. The whole plant, leaves, seeds, and aerial parts were the most useful plant parts in natural preparation in Saudi traditional medicine with a percentage of 29%, 28%, 7%, and 5% respectively as reported in the present review work. The present review work gives big data about medicinal plants used in traditional medicine in the Kingdom of Saudi Arabia including data about plant species, used parts, preparation method as well as medical uses.     

Comparing diversity levels in environmental samples: DNA sequence capture and metabarcoding approaches using 18S and COI genes

Environmental DNA studies targeting multiple taxa using metabarcoding provide remarkable insights into levels of species diversity in any habitat. The main drawbacks are the presence of primer bias and difficulty in identifying rare species. We tested a DNA sequence‐capture method in parallel with the metabarcoding approach to reveal possible advantages of one method over the other. Both approaches were performed using the same eDNA samples and the same 18S and COI regions, followed by high throughput sequencing. Metabarcoded eDNA libraries were PCR amplified with one primer pair from 18S and COI genes. DNA sequence‐capture libraries were enriched with 3,639 baits targeting the same gene regions. We tested amplicon sequence variants (ASVs) and operational taxonomic units (OTUs) in silico approaches for both markers and methods, using for this purpose the metabarcoding data set. ASVs methods uncovered more species for the COI gene, whereas the opposite occurred for the 18S gene, suggesting that clustering reads into OTUs could bias diversity richness especially using 18S with relaxed thresholds. Additionally, metabarcoding and DNA sequence‐capture recovered 80%–90% of the control sample species. DNA sequence‐capture was 8x more expensive, nonetheless it identified 1.5x more species for COI and 13x more genera for 18S than metabarcoding. Both approaches offer reliable results, sharing ca. 40% species and 72% families and retrieve more taxa when nuclear and mitochondrial markers are combined. eDNA metabarcoding is quite well established and low‐cost, whereas DNA‐sequence capture for biodiversity assessment is still in its infancy, is more time‐consuming but provides more taxonomic assignments.     

The role of extracellular matrix in biomechanics and its impact on bioengineering of cells and 3D tissues

The cells and tissues of the human body are constantly exposed to exogenous and endogenous forces that are referred to as biomechanical cues. They guide and impact cellular processes and cell fate decisions on the nano-, micro- and macro-scale, and are therefore critical for normal tissue development and maintaining tissue homeostasis. Alterations in the extracellular matrix composition of a tissue combined with abnormal mechanosensing and mechanotransduction can aberrantly activate signaling pathways that promote disease development. Such processes are therefore highly relevant for disease modelling or when aiming for the development of novel therapies.In this mini review, we describe the main biomechanical cues that impact cellular fates. We highlight their role during development, homeostasis and in disease. We also discuss current techniques and tools that allow us to study the impact of biomechanical cues on cell and tissue development under physiological conditions, and we point out directions, in which in vitro biomechanics can be of use in the future.     

Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography

Glucose transporter 2 (GLUT2) is involved in glucose uptake by hepatocytes, pancreatic beta cells, and absorptive cells in the intestine and proximal tubules in the kidney. Pancreatic GLUT2 also plays an important role in the mechanism of glucose-stimulated insulin secretion. In this study, novel Fluorine-18-labeled streptozotocin (STZ) derivatives were synthesized to serve as glycoside analogs for in-vivo GLUT2 imaging. Fluorine was introduced to hexyl groups at the 3′-positions of the compounds, and we aimed to synthesize compounds that were more stable than STZ. The nitroso derivatives exhibited relatively good stability during purification and purity analysis after radiosynthesis. We then evaluated the compounds in PET imaging and ex-vivo biodistribution studies. We observed high levels of radioactivity in the liver and kidney, which indicated accumulation in these organs within 5 min of administration. In contrast, the denitroso derivatives accumulated only in the kidney and bladder shortly after administration. Compounds with nitroso groups are thus expected to accumulate in GLUT2-expressing organs, and the presence of a nitroso group is essential for in-vivo GLUT2 imaging.     

湖南蓝山县端午药市的瑶药调查

中国南方一些少数民族地区民间“端午药市”流传至今,体现了民族医药的独具特色及其深远影响。为了解瑶族端午药市交易现状和发掘民族医药传统知识,采用民族植物学等方法对湖南省蓝山县端午药市进行调查,完成包括基原、地方名、药用部位、用途和用法、出现频度等内容的药用植物编目。结果表明:蓝山县端午药市药用植物种类丰富,共收集鉴定103科 222属262种,药用植物种类广泛分布于各科和各属中,其中种类较多的科有五加科(11种)、茜草科(11种)、菊科(11种)、百合科(10种)、唇形科(9种)、蝶形花科(8种)、芸香科(7种)。药市药浴植物畅销且种类多样,达94种,占总数的35.9%,体现瑶族在治疗疾病上以预防保健为主的理念。经统计药市上均未被国家药典和地方标准收录的药用植物有131种,占总数的50.2%,成为发掘新药源、新用途的潜在资源。对端午药市售药者年龄的调查发现,售药者的年龄主要集中在50～59岁间,占总人数的67%,40岁以下的仅占总人数的3%,可见民族药用传统知识的传承存在传承人老龄化、潜在传承人数量锐减的现象。此外,还对药市交易药用植物的种类组成和民族药用特色进行分析,探讨了端午药市对药用传统知识保护与传承的影响,并对蓝山端午药市的可持续发展提出了建议。     

消痰化瘀利窍中药组方对改善慢性间歇性低氧大鼠心肌纤维化的作用及其机制*

目的: 探讨转化生长因子-β(TGF-β)信号通路在消痰化瘀利窍中药组方(XC)对改善慢性间歇性低氧(CIH)大鼠心肌纤维化中的作用。方法: 40只SD 大鼠,随机分为常氧组(Normoxia)、常氧+中药干预组(TCMC)、慢性间歇性低氧模型组(CIH)、CIH +中药干预组(TCMC+CIH),每组10只。通过向舱内充入氮气,使舱内氧体积分数在90 s内从21%下降到9%,随后90 s再充氧气使舱内氧体积分数逐渐上升到21%为一循环建立CIH模型。CIH 与 TCMC+CIH 组大鼠置于CIH装置, Normoxia 和TCMC组大鼠置于正常氧舱。此外TCMC+CIH 与 TCMC 组大鼠于每日XC生药(24 g/kg)煎制灌胃,而 CIH 组与 Normoxia 组大鼠给予等体积生理盐水。造模结束后,天狼星红染色观察大鼠心肌间质内胶原沉积情况;Western blot 法检测大鼠心肌间质中 CollagenⅠ、Collagen Ⅲ、Fibronectin、TGF-β、p-Smad2、p-Smad3的蛋白表达水平。采用Q-PCR法检测基质金属蛋白酶2(MMP-2)和基质金属蛋白酶抑制因子 2 (TIMP-2) 的 mRNA表达水平。结果: 与正常组比较,CIH大鼠心肌组织出现明显胶原的沉积,CollagenⅠ、Collagen Ⅲ和Fibronectin蛋白表达明显增多(P均＜0.01),TGF-β、p-Smad2、p-Smad3蛋白表达水平也明显增高(P均＜0.01);CIH大鼠心肌组织TIMP-2 mRNA上调导致MMP-2 mRNA明显减少(P均＜0.01)。给予XC干预后,CIH大鼠心肌组织胶原沉积明显减少,CollagenⅠ、Collagen Ⅲ和Fibronectin蛋白表达明显降低(P＜0.05,P＜ 0.01,P＜0.05);CIH大鼠心肌组织中TGF-β、p-Smad2、p-Smad3蛋白表达水平明显降低(P＜0.01,P＜0.05,P＜ 0.01)。心肌组织中TIMP-2明显基因减少致MMP-2增多(P均＜0.05)。 结论: 消痰化瘀利窍中药组方可抑制CIH大鼠心肌纤维化的形成,进而改善CIH大鼠心肌功能。其机制与该中药组方下调TGF-β/ Smad2/3信号通路及下调TIMP-2mRNA有关。     

Synthesis and evaluation of new 1-oxa-8-azaspiro[4.5]decane derivatives as candidate radioligands for sigma-1 receptors

We report the design, synthesis, and evaluation of a series of 1-oxa-8-azaspiro[4.5]decane and 1,5-dioxa-9-azaspiro[5.5]undecane derivatives as selective σ₁ receptor ligands. All seven ligands exhibited nanomolar affinity for σ₁ receptors (K_i(σ₁) = 0.47 – 12.1 nM) and moderate selectivity over σ₂ receptors (K_i(σ₂)/ K_i(σ₁) = 2 – 44). Compound 8, with the best selectivity among these ligands, was selected for radiolabeling and further evaluation. Radioligand [¹⁸F]8 was prepared via nucleophilic ¹⁸F-substitution of the corresponding tosylate precursor, with an overall isolated radiochemical yield of 12–35%, a radiochemical purity of greater than 99%, and molar activity of 94 – 121 GBq/μmol. Biodistribution studies of [¹⁸F]8 in mice demonstrated high initial brain uptake at 2 min. Pretreatment with SA4503 resulted in significantly reduced brain-to-blood ratio (70% − 75% at 30 min). Ex vivo autoradiography in ICR mice demonstrated high accumulation of the radiotracer in σ₁ receptor-rich brain areas. These findings suggest that [¹⁸F]8 could be a lead compound for further structural modifications to develop potential brain imaging agents for σ₁ receptors.     

Development of a potent and orally active activator of adenosine monophosphate-activated protein kinase (AMPK), ASP4132, as a clinical candidate for the treatment of human cancer

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology. Structural optimization of lead compound 2, a new type of AMPK activator with potent AMPK activation activity and attractive selective growth inhibition against human cancer cells, improved aqueous solubility, metabolic stability and animal pharmacokinetics (PK) and culminated in the identification of (5-{1-[(6-methoxypyridin-3-yl)methyl]piperidin-4-yl}-1H-benzimidazol-2-yl)(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methanone ditosylate, ASP4132 (28). Studies on ASP4132 had advanced to clinical trials for the treatment of cancer.     

Common plasma protein marker LCAT in aggressive human breast cancer and canine mammary tumor

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymphnode-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.