The genus Inula and their metabolites: from ethnopharmacological to medicinal uses.

The genus Inula comprises more than one hundred species widespread in temperate regions of Europe and Asia. Uses of this genus as herbal medicines have been first recorded by the Greek and Roman ancient physicians. In the Chinese Pharmacopoeia, from the 20 Inula spp. distributed in China, three are used as Traditional Chinese medicines, named Tumuxiang, Xuanfuhua and Jinfeicao. These medicines are used as expectorants, antitussives, diaphoretics, antiemetics, and bactericides. Moreover, Inula helenium L. which is mentioned in Minoan, Mycenaean, Egyptian/Assyrian pharmacotherapy and Chilandar Medical Codex, is good to treat neoplasm, wound, freckles and dandruff. Many other Inula spp. are used in Ayurvedic and Tibetan traditional medicinal systems for the treatment of diseases such as bronchitis, diabetes, fever, hypertension and several types of inflammation. This review is a critical evaluation of the published data on the more relevant ethnopharmacological and medicinal uses of Inula spp. and on their metabolites biological activities. This study allows the identification of the ethnopharmacological knowledge of this genus and will provide insight into the emerging pharmacological applications of Inula spp. facilitating the prioritirization of future investigations. The corroboration of the ethnopharmacological applications described in the literature with proved biological activities of Inula spp. secondary metabolites will also be explored. The major scientific databases including ScienceDirect, Medline, Scopus and Web of Science were queried for information on the genus Inula using various keyword combinations, more than 180 papers and patents related to the genus Inula were consulted. The International Plant Name Index was also used to confirm the species names. Although the benefits of Inula spp. are known for centuries, there are insufficient scientific studies to certify it. Most of the patents are registered by Chinese researchers, proving the traditional use of these plants in their country. Although a total of sixteen Inula species were reported in the literature to have ethnopharmacological applications, the species Inula cappa (Buch.-Ham. ex D.Don) DC., Inula racemosa Hook.f., Inula viscosa (L.) Aiton [actually the accepted name is Dittrichia viscosa (L.) Greuter], Inula helenium, Inula britannica L. and Inula japonica Thunb. are the most frequently cited ones since their ethnopharmacological applications are vast. They are used to treat a large spectrum of disorders, mainly respiratory, digestive, inflammatory, dermatological, cancer and microbial diseases. Fifteen Inula spp. crude extracts were investigated and showed interesting biological activities. From these, only 7 involved extracts of the reported spp. used in traditional medicine and 6 of these were studied to isolate the bioactive compounds. Furthermore, 90 bioactive compounds were isolated from 16 Inula spp. The characteristic compounds of the genus, sesquiterpene lactones, are involved in a network of biological effects, and in consequence, the majority of the experimental studies are focused on these products, especially on their cytotoxic and anti-inflammatory activities. The review shows the chemical composition of the genus Inula and presents the pharmacological effects proved by in vitro and in vivo experiments, namely the cytotoxic, anti-inflammatory (with focus on nitric oxide, arachidonic acid and NF-κB pathways), antimicrobial, antidiabetic and insecticidal activities. Although there are ca. 100 species in the genus Inula, only a few species have been investigated so far. Eight of the sixteen Inula spp. with ethnopharmacological application had been subjected to biological evaluations and/or phytochemical studies. Despite Inula royleana DC. and Inula obtusifolia A. Kerner are being used in traditional medicine, as far as we are aware, these species were not subjected to phytochemical or pharmacological studies. The biological activities exhibited by the compounds isolated from Inula spp., mainly anti-inflammatory and cytotoxic, support some of the described ethnopharmacological applications. Sesquiterpene lactone derivatives were identified as the most studied class, being britannilactone derivatives the most active ones and present high potential as anti-inflammatory drugs, although, their pharmacological effects, dose-response relationship and toxicological investigations to assess potential for acute or chronic adverse effects should be further investigated. The experimental results are promising, but the precise mechanism of action, the compound or extract toxicity, and the dose to be administrated for an optimal effect need to be investigated. Also human trials (some preclinical studies proved to be remarkable) should be further investigated. The genus Inula comprises species useful not only in medicine but also in other domains which makes it a high value-added plant.

Seca AM ，Grigore A ，Pinto DC ，Silva AM ... -  《-》

A review of the botany, traditional uses, phytochemistry, and pharmacology of the Flos Inulae.

Plants of the genus Inula have long been used as an ethnomedicine in Asia, Europe, and North America for its high medicinal value and health benefits. Inula japonica Thunb. (I. japonica) and Inula britanica L. (I. britanica) are included in Chinese Pharmacopoeia (2020 edition) as the traditional Chinese medicine Flos inulae (FI). In TCM, FI tastes bitter, pungent, and salt, with warm nature and has the functions of water removal, reduction in nausea, and prevention of vomiting and is often used for cold-related coughs, sputum, wheezing coughs, vomiting, belching and other related diseases. In addition, Inula japonica Thunb is used as a botanical medicine in Korea and Inula britannica L. is also used as a traditional plant medicine in Iran. This paper collects the relevant research literature (1970-2021) and provides a systematic summary of the botany, ethnopharmacology, processing, phytochemistry, pharmacology, toxicity, analytical methods and quality control of FI to explore its potential and expand its scope for better clinical application. Information on Inula japonica Thunb. and Inula britanica L. was collected from scientific databases (1970-2021), including Google Scholar, Baidu Scholar, Springer, PubMed, CNKI and Wan Fang DATA. Information was also collected from classic books of Chinese herbal medicine and Ph.D. and M.Sc. theses. More than 200 chemical compounds have been isolated from Inula japonica Thunb. and Inula britanica L., including sesquiterpenes, flavonoids, volatile oils, triterpenoids, diterpenoid glycosides, monoterpenoids, polysaccharides, steroid and small molecule acids. Based on a wide variety of chemically active ingredients, FI has a wide range of pharmacological effects. Modern pharmacological research has proven that the pharmacological effects of FI include anti-inflammatory, antitumor, antioxidant, antiallergy, antidiabetic, blood lipid reduction, skin whitening, liver protection, anticonstipation, and antinociceptive effects. FI is a very important traditional Chinese herbal medicine with anti-inflammatory antitumor, antioxidant, antiallergy, antidiabetic and other pharmacological effects that can treat a variety of related diseases. This paper summarizes the botany, ethnopharmacology, processing, phytochemistry, pharmacology, toxicity, analytical methods, and quality control of FI. However, the research on the processing, toxicity and quality control of FI is currently too shallow, especially concerning the relationship between the changes in active components before and after processing and the changes in its pharmacological action, which remains unclear. There are few toxicity experiments conducted with FI, so it is impossible to evaluate the safety of FI objectively and impartially. There are also few studies on the material basis and doses of FI causing toxicity and side effects, and more in-depth and concrete researches should be carried out in the future regarding these aspects. Furthermore, to ensure effective and safe clinical medication, we should also pay attention to the mixed use of FI in various regions of China to control the quality of the FI plant.

Yang L ，Wang X ，Hou A ，Zhang J ，Wang S ，Man W ，Yu H ，Zheng S ，Wang Q ，Jiang H ，Kuang H ... -  《-》

A review of the medicinal uses, phytochemistry and pharmacology of the genus Sapium.

Several species from the genus Sapium possess a broad range of medicinal properties and they have been used as traditional medicines by indigenous groups in several regions such as Malaysia, Africa, Southern China and Bolivia. Most of the species reported to possess therapeutic effects which are used for the treatment of skin-related diseases such as eczema and dermatitis, but they may also be used for overstrain, lumbago, constipation and hernia. Species of this genus are also used to treat wounds and snake bites. In addition, the saps/latex of Sapium glandulosum, Sapium indicum and Sapium sebiferum have/has toxic effects and are used as bird and fish poisons. This review discusses the current knowledge of the medicinal uses, phytochemistry, biological activities and toxicities of species from the genus Sapium to reveal their therapeutic potentials and gaps offering opportunities for future research. This review is based on a literature study of scientific journals and books from libraries and electronic sources, such as ScienceDirect, PubMed and ACS. As many as 65 compounds are included in this review. They belong to different classes of compounds including flavonoids, terpenoids and several other types of compounds, such as alkaloids, phenolic acids and amides. The pharmacological studies revealed that various types of preparations, extracts and single compounds of species from this genus exhibited a broad spectrum of biological activities including antioxidant, antimicrobial, anti-inflammatory and cytotoxic activities. However, Sapium glandulosum, Sapium indicum and Sapium sebiferum were reported to possess toxic effects and Sapium sebiferum was found to contain phorbol esters acting as a tumor-promoting agent. The genus Sapium consists of 23 accepted (high confidence) species. However, only very few of species have been phytochemically and pharmacologically studied. There is great potential to discover new chemical constituents from this genus because only a few species have been phytochemically investigated thus far. Only 27 compounds of 65 identified compounds have been studied for their biological activities. Several extracts and single compounds from this genus were reported to exhibit interesting biological activities such as antimicrobial, antioxidant and cytotoxic effects. Furthermore, the toxicity studies of some phorbol esters suggested that the compounds acted as potential tumor-promoting agents by stimulating protein kinase C. This is an interesting fact in which a plant with medicinal properties also possesses toxic effects as well. Therefore, more clinical studies on the toxicity of the extracts of the plants and the compounds isolated from this genus are also crucial to ensure their safety and to assess their eligibility for use as sources for modern medicines.

Al Muqarrabun LM ，Ahmat N ，Aris SR 《-》

Medicinal plants from the genus Acalypha (Euphorbiaceae)--a review of their ethnopharmacology and phytochemistry.

Acalypha is the fourth largest genus of the Euphorbiaceae family with approximately 450-570 species. Several Acalypha species are used as medicinal plants in Africa and in the Mascarene Islands. Almost every part of the plant including the leaves, stem and roots are used as traditional remedies to treat and manage a panoply of ailments. However, there is no updated compilation of traditionally important medicinal plants from the Acalypha genus. The present review therefore, endeavors to provide for the first time an updated compilation of documented ethnopharmacological information in relation to the ethnomedicinal, ethnoveterinary, zoopharmacognosy, phytochemistry and biological activities of medicinal plants from the Acalypha genus which can subsequently open new perspectives for further pharmacological research. A literature search was performed on Acalypha species using ethnobotanical text books and scientific databases such as Pubmed, Scopus, EBSCO, Google Scholar and other web sources such as records from PROTA, PROSEA, and Botanical Dermatology Database. The Plant List, International Plant Name index and Kew Botanical Garden Plant name databases were used to validate scientific names. Plants from Acalypha genus are traditionally used in the treatment and/or management of diverse ailments such as diabetes, jaundice, hypertension, fever, liver inflammation, schistosomiasis, dysentery, respiratory problems including bronchitis, asthma and pheumonia as well as skin conditions such as scabies, eczema and mycoses. Approximately 124 species were listed in ethnobotanical studies with some botanical description and others mentioned from different web sources. However, only 40 species have been included in the present review due to the unavailability of ethnopharmacological data on the remaining species. Among the 40 cited species, 30 were traditionally used for the treatment and/or management of approximately 70 human diseases or health conditions. Two species, Acalypha alnifolia and Acalypha fruticosa are used as insecticides and sand fly repellent respectively. Only 2 species (Acalypha fruticosa and Acalypha indica) are used in ethnoveterinary practice and have similar human and veterinary applications. In zoopharmacognosy, only Acalypha ornata has been mentioned. Natives from Africa, Central America, North America, Southern China, India, Bangladesh, Papua New Guinea and Mascarenes islands utilize Acalypha species as ethnomedicine. Traditionally used Acalypha species have been reported to possess at least one of the following biological activities: antimicrobial, anti-diabetic, antioxidant, anti-inflammatory, larvidal, pupicidal, hepatoprotective, anticancer, leishmanicidal, antihyperglycemic, antihypertensive, anti-venom, analgesic, anthelmintic, antiemetic, laxative, expectorant, diuretic, post-coital antifertility effects and wound healing. A total of 167 compounds have been identified from 19 species, with 16 from eight species were reported to be bioactive. The present review represents 32.3% of species from the Acalypha genus and can be considered as the first compilation of ethnopharmacologically useful plants from this genus. There is a great potential to discover new biologically active phytochemicals from the Acalypha genus because only few species have been studied comprehensively. Therefore, the clinical evaluation of species from this genus is warranted in future studies to confirm the ethnomedicinal claims and for the safety approval of therapeutic applications.

Seebaluck R ，Gurib-Fakim A ，Mahomoodally F 《-》

The genus Commiphora: a review of its traditional uses, phytochemistry and pharmacology.

The resinous exudates of the Commiphora species, known as 'myrrh', are used in traditional Chinese medicine for the treatment of trauma, arthritis, fractures and diseases caused by blood stagnation. Myrrh has also been used in the Ayurvedic medical system because of its therapeutic effects against inflammatory diseases, coronary artery diseases, gynecological disease, obesity, etc. Based on a comprehensive review of traditional uses, phytochemistry, pharmacological and toxicological data on the genus Commiphora, opportunities for the future research and development as well as the genus' therapeutic potential are analyzed. Information on the Commiphora species was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar and Web of Science) and a library search for articles published in peer-reviewed journals. Furthermore, information also was obtained from some local books on ethnopharmacology. This paper covers the literature, primarily pharmacological, from 2000 to the end of December 2011. The resinous exudates from the bark of plants of the genus Commiphora are important indigenous medicines, and have a long medicinal application for arthritis, hyperlipidemia, pain, wounds, fractures, blood stagnation, in Ayurvedic medicine, traditional Chinese medicine and other indigenous medical systems. Phytochemical investigation of this genus has resulted in identification of more than 300 secondary metabolites. The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effects, including antiproliferative, antioxidant, anti-inflammatory and antimicrobial. The bioactive steroids guggulsterones have attracted most attention for their potent hypolipidemic effect targeting farnesoid X receptor, as well as their potent inhibitory effects on tumor cells and anti-inflammatory efficiency. The resins of Commiphora species have emerged as a good source of the traditional medicines for the treatment of inflammation, arthritis, obesity, microbial infection, wound, pain, fractures, tumor and gastrointestinal diseases. The resin of C. mukul in India and that of C. molmol in Egypt have been developed as anti-hyperlipidemia and antischistosomal agents. Pharmacological results have validated the use of this genus in the traditional medicines. Some bioassays are difficult to reproduce because the plant materials used have not been well identified, therefore analytical protocol and standardization of extracts should be established prior to biological evaluation. Stem, bark and leaf of this genus should receive more attention. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from the genus Commiphora.

Shen T ，Li GH ，Wang XN ，Lou HX ... -  《-》