Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH. Graphical Abstract

Targeting Reactive Oxygen Species in Atherosclerosis via Chinese Herbal Medicines

Cardio-cerebrovascular disease (CCVD) has become the leading cause of human mortality with the coming acceleration of global population aging. Atherosclerosis is among the most common pathological changes in CCVDs. It is also a multifactorial disorder; oxidative stress caused by excessive production of reactive oxygen species (ROS) has become an important mechanism of atherosclerosis. Chinese herbal medicine (CHM) is a major type of natural medicine that has made great contributions to human health. CHMs are increasingly used in the auxiliary clinical treatment of atherosclerosis. Although their mechanism of action is unclear, CHMs can exert a variety of antiatherosclerosis effects by regulating intracellular ROS. In this review, we discussed the mechanism of ROS regulation in atherosclerosis and analyzed the role of CHMs in the treatment of atherosclerosis via ROS.

Biological composition analysis of a natural medicine, Faeces Vespertilionis, with complex sources using DNA metabarcoding

Faeces Vespertilionis is a commonly used fecal traditional Chinese medicine. Traditionally, it is identified relying only on morphological characters. This poses a serious challenge to the composition analysis accuracy of this complex biological mixture. Thus, for quality control purposes, an accurate and effective method should be provided for taxonomic identification of Faeces Vespertilionis. In this study, 26 samples of Faeces Vespertilionis from ten provinces in China were tested using DNA metabarcoding. Seven operational taxonomic units (OTUs) were detected as belonging to bats. Among them, Hipposideros armiger (Hodgson, 1835) and Rhinolophus ferrumequinum (Schober and Grimmberger, 1997) were the main host sources of Faeces Vespertilionis samples, with average relative abundances of 59.3% and 24.1%, respectively. Biodiversity analysis showed that Diptera and Lepidoptera were the most frequently consumed insects. At the species level, 19 taxa were clearly identified. Overall, our study used DNA metabarcoding to analyze the biological composition of Faeces Vespertilionis, which provides a new idea for the quality control of this special traditional Chinese medicine.

Tanshinone IIA: New Perspective on the Anti-Tumor Mechanism of A Traditional Natural Medicine

The search for natural and efficacious antineoplastic drugs, with minimal toxicity and side effects, is an important part of antitumor drug research and development. Tanshinone IIA is the most evaluated lipophilic active component of Salvia miltiorrhiza. Tanshinone IIA is a path-breaking traditional drug applied in cardiovascular treatment. It has also been found that tanshinone IIA plays an important role in the digestive, respiratory and circulatory systems, as well as in other tumor diseases. Tanshinone IIA significantly inhibits the proliferation of several types of tumors, blocks the cell cycle, induces apoptosis and autophagic death, in addition to inhibiting cell migration and invasion. Among these, the regulation of tumor-cell apoptosis signaling pathways is the key breakthrough point in several modes of antitumor therapy. The PI3K/AKT/MTOR signaling pathway and the JNK pathway are the key pathways for tanshinone IIA to induce tumor cell apoptosis. In addition to glycolysis, reactive oxygen species and signal transduction all play an active role with the participation of tanshinone IIA. Endogenous apoptosis is considered the main mechanism of tumor apoptosis induced by tanshinone IIA. Multiple pathways and targets play a role in the process of endogenous apoptosis. Tanshinone IIA can protect chemotherapy drugs, which is mainly reflected in the protection of the side effects of chemotherapy drugs, such as neurotoxicity and inhibition of the hematopoietic system. Tanshinone IIA also has a certain regulatory effect on tumor angiogenesis, which is mainly manifested in the control of hypoxia. Our findings indicated that tanshinone IIA is an effective treatment agent in the cardiovascular field and plays a significant role in antitumor therapeutics. This paper reviews the pharmacological potential and inhibitory effect of tanshinone IIA on cancer. It is greatly anticipated that tanshinone IIA will be employed as an adjuvant in the treatment of various cancers.

Molecular Docking of the Terpenes in Gorgonian Corals to COX-2 and iNOS Enzymes as Anti-Inflammatory

Background: The inflammatory pathway is induced by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes, so it requires the development of its inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), but they have side effects. Therefore, the discovery and development of natural medicine as a lead compound are needed. The gorgonian corals have been reported to contain cyclic diterpenes with anti-inflammatory activities. The specific anti-inflammatory inhibitor potential has not been reported regarding these secondary metabolites, whether in COX-2 or iNOS. Thus, the in silico method is the right alternative. Objective: This study aimed to determine the potency of fifteen terpenes of the various gorgonian corals to COX-2 and iNOS enzymes as an anti-inflammatory Methods: Molecular docking was performed using ChemDraw Ultra 12.0, Chem3D Pro 12.0, Biovia Discovery Studio 2016 Client®, Autodock Tools 4.2, prediction pharmacokinetics (Pre-ADMET), and oral administration (Lipinski rule of five). Results: Potential terpenes based on ΔG (kcal/mol) and Ki (nM) to COX-2 were gyrosanol B (-10,32; 27,15), gyrosanol A (-10,20; 33,57), echinolabdane A (-9,81; 64,76). Only nine terpenes were specific to COX-2 active sites, while for iNOS were palmonine F (-7.76; 2070), briarenol C (-7.55; 2910), and all test compounds binding to the iNOS active sites. Pre-ADMET prediction obtained that HIA was very excellent (70–100%), Caco-2 had moderate permeability (4–70 nm sec-1), and PPB had strong binding (> 90%). Eight terpenes qualified for the Lipinski rule of five. Conclusion: NOS was a specific target for terpenes based on the free energy of binding (ΔG).

Analysis and Characterization of Quality Systems in the Natural Medicinal Products Industry in Costa Rica and the World

The use of natural products has been a practice carried out by people throughout history to take care of their health and to alleviate a wide variety of ailments. The reasons for the use of natural medicine at this time, with so many advances in pharmacology, are varied, among which are the dissatisfaction of the immediate needs of people to feel better about themselves and the economic factor. It must be considered that not everything natural is good. Therefore, the products manufactured and distributed under the line of Natural Medicinal Products must go through a verification and certification process, ensuring that they contain sufficient information on their composition and effects to avoid the risks that they may bring to those who consume them. This research describes good practices in the manufacture of natural products and shows the establishment of a Quality Management System in the pharmaceutical industry in different countries of the world. Finally, the use of natural products in Costa Rica is detailed, certain aspects to establish a Quality Management System in the country, as well as its importance.

Effect of Morus alba leaf extract dose on lipid oxidation, microbiological stability, and sensory evaluation of functional liver pâtés during refrigerated storage

Mulberry (Morus alba L.), and above all the extract from the leaves of this plant, is a natural medicine that has been used in traditional medicine for hundreds of years. Mulberry leaves contains polyphenol compounds: flavonoids, coumarins, numerous phenolic acids, as well as terpenes and steroids. The antioxidant effect of these compounds may be beneficial to the fat fraction of meat products, thereby increasing their functional qualities. The aim of the study was to evaluate the effectiveness of the use of mulberry water leaf extract, as an additive limiting adverse fat changes and affecting the functionality in model liver pâtés. Pork pâtés were prepared by replacing 20% of animal fat with rapeseed oil (RO), and water extract of mulberry leaves was added in the proportion of 0.2%, 0.6% and 1.0%. It has been shown that the addition of mulberry leaf extract delayed the appearance of primary and secondary fat oxidation products. The most effective antioxidant effect during 15-day storage was observed in the sample with the addition of 0.6% and 1.0% water mulberry leaf extract. These samples also showed inhibiting activity against angiotensin-converting enzymes and cholinesterase’s. During storage, the tested pâtés had a high sensory quality with unchanged microbiological quality. Mulberry leaf extract can be an interesting addition to the production of fat meat products, delaying adverse changes in the lipid fraction and increasing the functionality of products.

Pharmacognostical Profile of Gymnema sylvestre and its Anti-Hyperglycemic Activity

In this paper explored the pharmacognostical profile of gymnema sylvestre and its anti-hyperglycemic activity has been documented well with references. The importance of the species in Ayurveda has been highlighted. The bioactive components like gymnema sylvestre has a variety of secondary metabolites, including oleanane, gymnemic acid, gymnemasides (A-F), gymnemic acid (IXVIII) homologue, gymnemic acid A1 and its derivatives, triterpenoidsaponin, al has been clearly includedin the review kaloid (Conduritol-A), polypeptide (Gurmarin), and gymnemasaponins. This study has provided the groundwork for developing a pharmacognostical profile of medicinal plant growers and collectors. The goal of this review study is to provide a regional profile of the indigenous knowledge system for medicinal plant usage and cultural behaviors related to healing. This study aids in the identification of novel ethnomedicinal plant species in the study region, which may lead to the development of new medicines. The plant toxicity test results indicated that it may be used as an alternative to diabetes therapy with no or little adverse effects. This study confirms the conventional use of indigenous plant-derived natural medicine for treating diabetes mellitus. The study also highlighted the efficacy of "Ayurveda" which is an ancient tradition, used in some parts of India. This ancient concept should be carefully evaluated in the light of modern medical science and can be utilized partially if found suitable. I hope that this kind of research will be useful to future researchers as per their needs.

Chemical, Cytotoxic, and Anti-Inflammatory Assessment of Honey Bee Venom from Apis mellifera intermissa

The venom from Apis mellifera intermissa, the main honey bee prevailing in Morocco, has been scarcely studied, despite its known potential for pharmacological applications. In the present work, we investigated the composition, the anti-inflammatory activity, and the venom’s cytotoxic properties from fifteen honey bee venom (HBV) samples collected in three regions: northeast, central, and southern Morocco. The chemical assessment of honey bee venom was performed using LC-DAD/ESI/MSn, NIR spectroscopy and AAS spectroscopy. The antiproliferative effect was evaluated using human tumor cell lines, including breast adenocarcinoma, non-small cell lung carcinoma, cervical carcinoma, hepatocellular carcinoma, and malignant melanoma. Likewise, we assessed the anti-inflammatory activity using the murine macrophage cell line. The study provides information on the honey bee venom subspecies’ main components, such as melittin, apamin, and phospholipase A2, with compositional variation depending on the region of collection. Contents of toxic elements such as cadmium, chromium, and plumb were detected at a concentration below 5 ppm, which can be regarded as safe for pharmaceutical use. The data presented contribute to the first study in HBV from Apis mellifera intermissa and highlight the remarkable antiproliferative and anti-inflammatory effects of HBV, suggesting it to be a candidate natural medicine to explore.

Edible flowers: traditional and current use

Flowers have been part of human life since antiquity. Several civilizations have left the legacy of using flowers in art, natural medicine, as well as in cooking to color, flavor and embellish various dishes. Edible flowers (EF) are those that can be consumed without endangering consumer’s health. Although not all countries in the world use flowers for food, their use has increased in general, as well as the interest of researchers from different areas of knowledge, as they are considered new sources of nutrients and bioactive compounds. However, the safety of its use is still questioned due to the lack of more information about the maximum safe amount of daily intake. This review aimed to gather information about the traditional use of EF, safety in consumption and consumers’ perception of these products.