Genus Salacia Research Articles

Design and Synthesis of Sulfonium Derivatives: A Novel Class of α-Glucosidase Inhibitors with Potent In Vivo Antihyperglycemic Activities.

We report the first attempt of double-spot structural modification on a side-chain moiety of sulfonium-type α-glucosidase inhibitors isolated from genus Salacia. A series of sulfonium salts with benzylidene acetal linkage at the C3' and C5' positions were designed and synthesized. In vitro enzyme inhibition evaluation showed that compounds with a strong electron-withdrawing group attached at the ortho position on the phenyl ring present stronger inhibitory activities. Notably, the most potent inhibitor 21b (1.0 mpk) can exhibit excellent hypoglycemic effects in mice, which can still compete with those of acarbose (20.0 mpk). Molecular docking of 21b demonstrated that besides conventional interacting patterns, the newly introduced benzylidene acetal moiety plays an important role in anchoring the whole molecule in a concave pocket of the enzyme. The successful identification of 21b as a lead compound for new drug discovery may provide a means for structure modification and diversification of the distinguished sulfonium-type α-glucosidase inhibitors.

Morphological and Qualitative Phytochemical Comparison of Selected <em>Salacia</em> Species in Lowland Wet Zone of Sri Lanka

Many medicinal plants in the world are in trouble from over harvesting and destruction of habitat. Population growth, urbanization and the unlimited collection from the wild are the causes for the over-exploitation of these natural resources. Therefore, the management of the traditional medicinal plant in Sri Lanka has become a matter of necessity too. The genus Salacia has great importance as it contains a high medicinal value that is mostly used in traditional medicine to cure diabetes. Scientific information and knowledge about them are scant and their current usage is limited relative to their economic potential. It is necessary to examine their morphology and chemical composition as they have received a less attention for conservation and management. In Sri Lanka, the genus Salacia is represented by five species and only Salacia chinensis, Salacia oblonga, and Salacia reticulata were considered in this study. A morphological study using the specimens collected from natural habitats was done. The selected Salacia species could be three different species in the same genus. Anatomical studies were carried out by obtaining stem cross-sections. It also revealed that there are differences in hypodermis of selected Salacia species too. Qualitative phytochemical screening by using the air-dried and powdered stems was carried out to identify the different chemical compounds in water. The study confirmed the presence of tannins, terpenoids, and saponin. TLC profiling of these species was carried out using methanol extracts and it showed different Rf values. Further, the generated results could be effectively utilized for the consistency of Salacia species for the improvement of the Sri Lankan pharmacopeia.

The genus Salacia (Celastraceae: Salaciodeae) in peninsular India

The genus Salacia (Celastraceae: Salaciodeae) in peninsular India is revised, wherein ten species are recognised. Eight species are endemic to the region. Salacia macrophylla and S. reticulata are excluded from the revision as occurrence of both the species is doubtful in mainland India. Salacia macrosperma exhibits great variation in leaf shape, flower number, pedicel length and fruit texture, hence the morphologically similar species S. beddomei and S. vellaniana are relegated to its synonymy. Descriptions, photographs, and pen and ink as well as colour drawings of all recognised Salacia species are provided with an artificial key, updated nomenclature, and synonymy. Distribution and IUCN Red list categories and criteria are also discussed. Seven binomials, S. fruticosa, S. macrophylla, S. macrosperma, S. oblonga, S. ovalis, Tontelea prinoides and Johnia coromadeliana are lectotypified.

Elicitor-mediated enhancement of biomass, polyphenols, mangiferin production and antioxidant activities in callus cultures of Salacia chinensis L.

The present investigation aimed to improve callus biomass, polyphenolic content, biosynthesis of mangiferin and biological potential following application of different elicitor treatments for medicinally important Salacia chinensis L. The leaf-derived callus cultures were established on Murashige and Skoog's (MS) medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D: 2.0mg/l) and 6-benzylaminopurine (BAP: 1.5mg/l). These cultures were treated with different elicitors viz. jasmonic acid (JA), methyl jasmonate (MeJA) and yeast extracts (YE). The highest calli biomass (five-fold increase within 4weeks) was achieved when callus was treated with JA (75µM). The callus obtained on MS medium supplemented with 2,4-D (2.0mg/l), BAP (1.5mg/l) and treated with JA (75µM) displayed augmented values for total phenolics, flavonoids and mangiferin contents. Besides, same treatment elicits the calli for antioxidant properties as evaluated by 2,2-diphenyl-2-picrylhydrazyl (DPPH), ferric-reducing antioxidant power (FRAP) and metal chelating assays. This is the first report on the elicitation study in genus Salacia and, therefore, the discoveries suggested that, S. chinensis calli might be a perfect source for large-scale production of industrially important secondary metabolites. Concurrently data provide accumulated information demonstrating its prominent antioxidant effect revealing its potential without disturbing natural resources.

ITS 2 and RNA secondary structure-based analysis reveals a clear picture on phylogeny of South Indian Salacia spp.

The genus Salacia (Celastraceae) consists of many important medicinal plants used mainly against type II diabetes. Segregation and delimitation of species is difficult based on morphological features alone. DNA barcoding is the most effective and emerging method of molecular identification. It was reported that ITS2 has better discriminating power in the genus Salacia in comparison to other barcode loci. This paper describe the analysis of sequence and structural information of ITS2 to discriminate the species of Salacia. A total of 8 species of Salacia in South India and the available sequences in NCBI database were taken for the present study. NJ method based phylogenetic trees were constructed using MEGAX with primary sequence as well as using sequence and secondary structural information. Primary structure based phylogeny did not give much information whereas the dendrogram based on sequence and structural information was more informative to decipher the phylogeny of South Asian species of Salacia. The present study revealed some interesting facts regarding the genus. Secondary structure of the ITS2 sequence of S. chinensis reported from Kerala differs consistently from that of S. chinensis reported from other parts of India and of South Asia. Probably the S. chinensis in Kerala, India has diverged a lot from the original S. chinensis. ITS2 sequence of S. reticulata reported from Sri Lanka was identical to S. chinensis reported by other groups from Thailand and Udupi, India. The molecular level identity of ITS2 sequence of S. chinensis with S. reticulata suggest merger of the two species. ITS2 sequence of S. beddomei is only reported from Kerala, India showed it to be identical to S. macrosperma. This observation points to a mistaken identity of S. beddomei which could be elusive from Kerala. Phylogenetic trees constructed based on sequence and structural features of ITS2 suggest that the ancestor species of S.chinensis diversified in two evolutionary lines. One line leads to the present day S. chinensis and the other line further diversified and lead to the rest of the present day Salacia species.

Dose-Dependent Suppression of Postprandial Hyperglycemia and Improvement of Blood Glucose Parameters by Salacia chinensis Extract: Two Randomized, Double-Blind, Placebo-Controlled Studies.

The number of diabetes mellitus and borderline diabetes cases is increasing and poses a serious problem worldwide. Plants of the genus Salacia are known to have α-glucosidase inhibitory activity and to lower postprandial hyperglycemia. Two randomized, double-blind, placebo-controlled clinical trials were conducted to evaluate the efficacy of Salacia chinensis extract. Study 1 was a single-dose crossover study of 150, 300, or 600 mg of Salacia extract or placebo to determine the dose dependency of the effect on postprandial hyperglycemia. The duration of the washout period between each experimental day was a minimum of 6 days. Study 2 was a 12-week, multiple-dose, parallel-group study to evaluate the effects of 600 mg/day of Salacia extract on blood glucose parameters. In Study 1, Salacia induced significant dose-dependent suppression of postprandial blood glucose, insulin, and their incremental area under the curve values. The dose of 600 mg appeared to have the most significant effect. In Study 2, Salacia significantly improved several blood glucose-related parameters, such as hemoglobin A1c, and glucose tolerance after glucose challenge. These results suggest that S. chinensis extract may have beneficial effects in patients with diabetes.

Reassessment of the Genus <i>Salacia</i> under IUCN Threatened Categories in Sri Lanka

Salacia comprises of five species in Sri Lanka S. acuminatissima, S. chinensis, S. diandra, S. oblonga and S. reticulata while around two hundred species are distributed in tropical countries worldwide. All five species recorded in Sri Lanka are listed under various threaten categories in the National Red List 2012.The present study was carried out to reassess their conservation status based on IUCN threatened categories using preliminary field observations and data in order to contribute to the national red listing with robust data. The species were evaluated based on the criteria B of the IUCN guidelines 2017.The conservation statuses of two Salacia species S. acuminatissima and S. chinensis have remained same as the previous conservation statuses determined at national level as Endangered (EN) and Near threatened (NT) respectively. However, S. diandra was upgraded to the category of Critically Endangered (CR). The statuses of S. oblonga and S. reticulata were downgraded from Endangered (EN) to Near threatened (NT). Conservation statuses obtained using preliminary data and the upgrading the status of a taxa and downgrading of the statuses of two taxa is of prime importance to prioritize conservation of the members of the Genus Salacia in globally.

Taxonomic identity, occurrence of six species of Salacia and first report on chromosome numbers of the Salacia chinensis L. and Salacia oblonga Wall ex Wight and Ern Var. from Western Ghats of Karnataka (India)

The genus Salacia is an important element of the forest flora of the Western Ghats of Karnataka and is well known for its anti-diabetic properties. The region hosts a wide diversity with several taxa. The genus is considered as a taxonomically difficult one due to the complexity and diversity in floral characteristics. The species is still poorly understood with respect to its cytological characteristics. The present study explicates the diversity and distribution of Salacia species in the Western Ghats of Karnataka. Here, we also present the first report of the chromosome numbers of the species Salacia chinensis L. and Salacia oblonga Wall ex Wight and Ern Var. and is different from those of other previously reported Celastraceae genera. Conservation status of Salacia species of the Western Ghats of Karnataka has also been revised in this study. The diversity of floral morphology, leaf morphology, fruit and seed morphology, stem and root morphology were elaborated along with a dichotomous key to the Western Ghats species. Morphological study in S. chinensis L., S. malabarica Gamble, S. oblonga Wall ex Wight and Ern Var, S. macrosperma Wight, S. reticulata Wight and S. gambleana Whiting and Kaul is done for the first time using descriptor analysis. The paper describes 73 morphological traits that appear to be at least partly genetically controlled and can be used as descriptors of Salacia species.

Genetic Structure and Diversity among Species of Salacia: An Endangered Medicinal Herb of Western Ghats, India

Salacia is one of the medicinally valuable genus, distributed throughout tropical areas which include India, Sri Lanka, Southern China and other Southern Asian Countries. The genus Salacia is represented by 21 species in India, among them eight species are recorded from the state of Karnataka in the Southern part of India. Despite its pharmaceutical importance, very little information exists about the genetic diversity of Salacia at molecular level. Hence the present study was carried out to evaluate the genetic among six species of Salacia namely S. chinensis, S. malabarica, S. oblonga, S. macrosperma, S. reticulata and S. gambleana with the help of ISSR marker analysis. Dendrogram and genetic distance were generated adopting Unweighted Paired Group Method with Arithmetic mean (UPGMA) in the NTSYS-pc software. Basic genetic parameters were calculated by analysing the genetic data with Pop gene 1.32 and GenAlEx 6.2 software. The overall polymorphism across the ten primers screened revealed 26 % polymorphism. A 60% polymorphism was scored for the primer UBC 841, whereas, no polymorphism was observed for primer UBC 840 and ISSR 6. The average observed heterozygosity was more than expected heterozygosity. Observed heterozygosity (Ho) ranged from 0.15 (UBC 841) to 0.38 (ISSR 6) with an average of 0.25, whereas expected heterozygosity (He) ranged from 0.10 (UBC 843) to 0.35 (ISSR 6) with an average of 0.23 for Salacia species. The higher heterozygosity pointed towards increased genetic diversity amongst the species. ISSR marker analysis showed high level of inter and intra population genetic differentiation.

Practical Route to Neokotalanol and Its Natural Analogues: Sulfonium Sugars with Antidiabetic Activities

AbstractAn efficient and divergent approach toward the synthesis of all four de‐O‐sulfonated sulfonium type α‐glucosidase inhibitors, originally isolated from plants of genus Salacia, is reported for the first time. The key strategy features a coupling reaction between thiol derivatives and a diiodide counterpart. The newly designed thiol coupling partner presents high chemical stability, while the diiodide partner could be easily obtained with increased overall yields compared with conventional routes. The intermolecular nucleophilic substitution reaction followed by a diastereoselective intramolecular cyclization provided the target five‐member sulfonium salt structure, which was connected in an α‐orientation to a polyhydroxylated side‐chain moiety.

Practical Route to Neokotalanol and Its Natural Analogues: Sulfonium Sugars with Antidiabetic Activities.

An efficient and divergent approach toward the synthesis of all four de-O-sulfonated sulfonium type α-glucosidase inhibitors, originally isolated from plants of genus Salacia, is reported for the first time. The key strategy features a coupling reaction between thiol derivatives and a diiodide counterpart. The newly designed thiol coupling partner presents high chemical stability, while the diiodide partner could be easily obtained with increased overall yields compared with conventional routes. The intermolecular nucleophilic substitution reaction followed by a diastereoselective intramolecular cyclization provided the target five-member sulfonium salt structure, which was connected in an α-orientation to a polyhydroxylated side-chain moiety.

Cytotoxic Triterpenes from Salacia crassifolia and Metabolite Profiling of Celastraceae Species.

The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both the extract and the purified triterpenes displayed pronounced cytotoxic activity against human cancer cell lines. The NCI-60 cell line screen revealed that compound 2 was the most active, with a mean GI50 of 0.17 μM, while compound 1 had a mean GI50 of 8.7 μM. A COMPARE analysis of the screening results showed that pristimerin is likely to be the main compound responsible for the cytotoxic activity of the extract (mean GI50 of 0.3 μg·mL−1). A targeted search for pristimerin and related derivatives using LC-MS/MS revealed the presence of pristimerin (2) and 6-oxopristimerol (3) in all Celastraceae species examined and in all plant parts tested, while vitideasin (4) was only detected in the genus Salacia.

A Systematic Survey, Taxonomic Study and Conservation of Genus Salacia (Celastraceae) in North Central Province of Sri Lanka

Genus Salacia is a climbing shrub comprised of nearly 200 species out of which, five have been reported in Sri Lanka. Salacia species are important components in many Ayurveda preparations and traditional medicine. Since S. reticultata and S. oblonga possess scientifically proven therapeutic benefits for an array of burning health issues, people tend to over exploit them from the wild to fulfill the existing demand. As a result, these two have become endangered in Sri Lanka. Therefore, recording existing populations in different agro-ecological regions with their abundance has become one of the key issues in conservation and sustainable use of these plants. Moreover, these species exhibit morphological plasticity and documented vegetative characters to differentiate one from the other are scares. The present study was launched to carry out a systematic survey and taxonomic study of different populations of Salacia species in the North Central province with the view of confirming taxonomic position of existing populations, documenting vegetative characters as there are overlapping morphological characters and flowering is seasonal and identifying unique populations for conservation. In the Systematic survey 28 localities out of which 15 are new records in the North Central Province where Salacia species were growing naturally were found. Representative samples were collected from twenty locations and identified, subsequently authenticated and used for the morphological study. Ninety morphological and anatomical characters of each population were scored by using standard methods. Methods for leaf clearing and wood maceration suitable for Genus Salacia were developed. A preliminary screening of phytochemicals was done using TLC. Leaf and stem extracts were obtained by cold extraction and Soxhlet method. TLC profiles were recorded under UV, using Anisaldehyde-sulphuric acid and Iodine vapour. Taxonomic relationships among collected samples were analyzed. Out of the ninety characters studied, fifty four could be identified as clear characters for species demarcation. Based on the study, eight samples could be clearly identified as S. reticulata, six as S. oblonga but the remaining six displayed a mixture of morphological characters of S. chinensis, S. reticulata and S. oblonga. The population collected from Ritigala (a new locality) showed deviation in characters from all others and hence need to draw the attention of conservationists. Keywords: S. reticulata, S. oblonga, Taxonomic relationship

Characterization and Comparison of Three Species of the Genus Salacia.

Some of the plant species of the genus Salacia are considered as an important anti-diabetic drug in ayurveda. Among them S. chinensis, S. fruticosa and S. oblonga possess great medicinal importance, mostly because of its promising anti-diabetic activity. The increasing demand of this drug, resulted in a huge decline in its availability and it is replaced by spurious ones mainly because of lack of adequate quality standards. There is now a felt need to develop a systematic approach for the authentication of these plants and to develop well-designed methodologies for its standardization. The present study focused on the Pharmacopoeial parameters like pharmacognostical characterization and preliminary phytochemical screening of these three species. which were found to be sufficient to evaluate the raw material and can also be used as reference standards for the quality control/quality assurance purposes. The pharmacognostic study revealed that there are specific diagnostic features for distinguishing these three species among themselves and also from other related species. The external morphology of these three species are also shows variation in their colour, odour and taste. Both the species of Salacia ie, S. chinensis is having bitter taste and S. fruticose is with astringent taste whereas S. oblonga has no characteristic taste of its own. The TLC profile showed similar pattern in S. chinensis and S. fruiticosa where as S. oblonga showed more band in the profile than that of the other two. This reveals that the S. chinensis and S. fruiticosa having similar compounds responsible for therapeutic efficacy, whereas S. oblonga has more chemical constituents.

Comparative Phytochemical Profiling and Quantification of Mangiferin Content in Species of Salacia from Southern Western Ghats of India

Many species of the genus Salacia L. are used in traditional Indian systems of medicines for their anti-diabetic potential. In this study, we carried out a comparative phytochemical evaluation of the roots of nine species of Salacia viz. S. agasthiamalana, S. beddomei, S. brunoniana, S. chinensis, S. fruticosa, S. gambleana, S. malabarica, S.oblonga and S. wayanadica, which are distributed in the Southern Western Ghats. Qualitative profiling showed the presence of different phytochemicals. Subsequently quantification of mangiferin, the prominent anti-diabetic molecule was carried out using HPLC in all these species. S. brunoniana (2.586 mg/g of dry root) showed maximum mangiferin content, followed by S. beddomei (2.195), S. chinensis (1.57), S. fruticosa (1.055), S. oblonga (0.305), S. agasthiamalana (0.086), S. malabarica (0.0296), S. gambleana (0.0218) and S. wayanadica (0.0005). The presence of mangiferin in S. agasthiamalana, S. beddomei, S. brunoniana, S. gambleana, S. malabarica and S. wayanadica, are reported for the first time. The study identified that S. brunoniana and S. beddomei could be the most promising raw material for anti-diabetic drug formulations based on mangiferin content.

Improvement in Human Immune Function with Changes in Intestinal Microbiota by Salacia reticulata Extract Ingestion: A Randomized Placebo-Controlled Trial.

Plants belonging to the genus Salacia in the Hippocrateaceae family are known to inhibit sugar absorption. In a previous study, administration of Salacia reticulata extract in rats altered the intestinal microbiota and increased expression of immune-relevant genes in small intestinal epithelial cells. This study aimed to investigate the effect of S. reticulata extract in human subjects by examining the gene expression profiles of blood cells, immunological indices, and intestinal microbiota. The results revealed an improvement in T-cell proliferation activity and some other immunological indices. In addition, the intestinal microbiota changed, with an increase in Bifidobacterium and a decrease in Clostridium bacteria. The expression levels of many immune-relevant genes were altered in blood cells. We concluded that S. reticulata extract ingestion in humans improved immune functions and changed the intestinal microbiota. Trial Registration: UMIN Clinical Trials Registry UMIN000011732

Species discrimination through DNA barcoding in the genus Salacia of the Western Ghats in India

The genus Salacia (Celastraceae) is a source of many important pharmaceutical chemicals used in the Ayurvedic system of medicine in India. Owing to morphological similarities between species, the taxonomy of Salacia is complex and not fully settled. To ensure quality and assured therapeutic effects in the raw drugs from the genus, proper identification at the species level is critical. The main objective of this study was to find suitable DNA barcodes that can accurately and efficiently identify the potential medicinal species of the genus. Among the barcode loci analyzed, ITS2 exhibited the highest interspecific divergence, followed by trnH‐psbA, matK and rbcL. A clear barcoding gap was evident for the ITS2 barcode region whereas it was less conspicuous for trnH‐psbA and matK. The ITS2 barcode could discriminate all the eight analyzed Salacia species with 100% accuracy. We therefore propose barcoding with ITS2 to confirm the taxonomic identity of the raw drugs in the market. Further, the ITS2 region can be recommended for biosystematic studies in the genus.

Genus Salacia: Chemical Composition, Antidiabetic Effect and other Bioactivities

The plants of Salacia genus (Celastraceae) have distribution in tropical areas, especially in regions of Asia as in India, Sri Lanka, Thailand and Indonesia, and in South America, as in Brazil. Around the world, about 120 species are known. Salacia`s species are known to elaborate secondary metabolites like anthocyanidines, catechins, phenolic acids, quinones, friedo-oleanones, quinonemethide and related triterpenoids (celastroloids). Biological activities have been reported for crude extracts, fractions and isolated compounds, which are mainly antidiabetic, antioxidant and anti-inflammatory. This review aims to identify key species, their chemical components, and the reported bioactivity as a guide to future research about this genus. Keywords: Biological actions, diabetes, phytochemistry, Salacia genus.

Unravelling the names, origins and chemistry of “muthis” used for male sexual disorders in KwaZulu-Natal, South Africa

In KwaZulu-Natal, most muthis (medicinal plants) associated with male sexual disorders go under the name uBangalala. Our research shows for the first time that the major plant sources for these preparations are three plants from the genus Eriosema (E. kraussianum, E. salignum and E. cordatum) and three plants from the genus Salacia (S. rehmannii, S. leptoclada and S. kraussii). Since it is the roots that contain the desired active components, and since these roots are purchased without “above-ground appendages” (i.e. leaves and stems), it posed a real challenge to bring together the root and appropriate leaf. However, this was overcome by excursions to the places of origin of the relevant plants. An interesting outcome of this task was the finding that S. rehmannii, not normally associated with KwaZulu-Natal, is quite widespread in the Maputaland Sandveld of this province in the form of S. rehmannii (KB) and S. rehmannii (SB). Indeed, these two plants are a major source of the much sought-after muthi, uBangalala.The active chemical components in the Eriosema plants are two closely-related pyranoisoflavones. The Salacia species mentioned above are rich in triterpene quinone methides, far-removed from the pyranoisoflavones present in the Eriosema series. According to the current literature, the major quinone methide, pristimerin, is used for a variety of ailments, but the evidence that it is associated with male sexual disorders is very tenuous. This, of course, raises the question whether the quinone methides, and particularly pristimerin, have hitherto untested aphrodisiac-like properties, or whether unknown minor components in the plant are responsible for perceived (but untested) sex-related activity.

Effect of NR-Salacia on post-prandial hyperglycemia: A randomized double blind, placebo-controlled, crossover study in healthy volunteers

Background:Salacia chinensis (S. chinensis) is widely distributed in India and Sri Lanka. Most of the species of genus Salacia are known to have effects on blood glucose levels; however, the effects of S. chinensis on glucose levels are seldom reported.Objective:To evaluate the oral hypoglycemic activity of NR- Salacia (1000 mg extract of S. chinensis) in healthy adults.Materials and Methods:Randomized, double-blind, placebo-controlled, cross-over study was conducted in healthy volunteers. Single dose of NR-Salacia (1000 mg extract of Salacia chinensis) and placebo were administered before carbohydrate-rich diet. A 6-point plasma glucose profile was performed at different time intervals up to 180 min.Results:NR-Salacia treatment significantly lowered plasma glucose level at 90 min, and the percentage reduction in glucose concentration was found to be 13.32 as compared to placebo group. A 33.85% decrease in the plasma glucose positive incremental area under curve (AUC) (0 to 180 min) was observed in comparison to placebo. No adverse events were recorded throughout the study period, except for some mild cases of abdominal discomforts like cramping and distention, vomiting, and headache in both placebo and NR-Salacia-treated groups.Conclusion:The study findings revealed that NR-Salacia lowered the post-prandial plasma glucose levels after a carbohydrate-rich meal and can be used as an oral hypoglycemic agent.