Cystathionine-β-synthase (CBS) catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of homocysteine (Hcy) in the kidney. Our recent study demonstrates that ischemia-reperfusion reduces the activity of CBS leading to Hcy accumulation in the kidney, which in turn contributes to renal injury. CBS is also capable of catalyzing the reaction of cysteine with Hcy to produce hydrogen sulfide (H2S), a gaseous molecule that plays an important role in many physiological and pathological processes. The aim of the present study was to examine the effect of ischemia-reperfusion on CBS-mediated H2S production in the kidney and to determine whether changes in the endogenous H2S generation had any impact on renal ischemia-reperfusion injury. The left kidney of Sprague-Dawley rat was subjected to 45-min ischemia followed by 6-h reperfusion. The ischemia-reperfusion caused lipid peroxidation and cell death in the kidney. The CBS-mediated H2S production was decreased, leading to a significant reduction in the renal H2S level. The activity of cystathionine-γ-lyase, another enzyme responsible for endogenous H2S generation, was not significantly altered in the kidney upon ischemia-reperfusion. Partial restoration of CBS activity by intraperitoneal injection of the nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide not only increased renal H2S levels but also alleviated ischemia-reperfusion-induced lipid peroxidation and reduced cell damage in the kidney tissue. Furthermore, administration of an exogenous H2S donor, NaHS (100 μg/kg), improved renal function. Taken together, these results suggest that maintenance of tissue H2S level may offer a renal protective effect against ischemia-reperfusion injury.

Our recent study (Prathapasinghe GA, Siow YL, O K. Am J Physiol Renal Physiol 292: F1354-F1363, 2007) indicates that homocysteine (Hcy) plays a detrimental role in ischemia-reperfusion-induced renal injury. Elevation of renal Hcy concentration during ischemia-reperfusion is attributed to reduced activity of cystathionine-beta-synthase (CBS) that catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of the majority of Hcy in the kidney. However, the mechanisms of impaired CBS activity in the kidney are unknown. The aim of this study was to investigate the effects of pH and nitric oxide (NO) on the CBS activity in the kidney during ischemia-reperfusion. The left kidney of a Sprague-Dawley rat was subjected to ischemia-reperfusion. The CBS activity was significantly reduced in kidneys subjected to ischemia alone (15-60 min) or subjected to ischemia followed by reperfusion for 1-24 h. The pH was markedly reduced in kidneys upon ischemia. Injection of alkaline solution into the kidney partially restored the CBS activity during ischemia. Further analysis revealed that reduction of CBS activity during reperfusion was accompanied by an elevation of NO metabolites (nitrate and nitrite) in the kidney tissue. Injection of a NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), restored the CBS activity in the kidneys subjected to ischemia-reperfusion. Treatment with PTIO could abolish ischemia-reperfusion-induced lipid peroxidation and prevent cell death in the kidney. These results suggested that metabolic acidosis during ischemia and accumulation of NO metabolites during reperfusion contributed, in part, to reduced CBS activity leading to an elevation of renal Hcy levels, which in turn, played a detrimental role in the kidney.

Hyperhomocysteinemia, a condition of elevated blood homocysteine level, is an independent risk factor for cardiovascular diseases. Hyperhomocysteinemia is also found in patients with liver diseases. However, the direct effect of homocysteine on liver injury is not well known. Folic acid supplementation is a promising approach for improving endothelial function in patients with hyperhomocysteinemia. The aim of this study was to investigate the direct effect of hyperhomocysteinemia on liver injury and whether folic acid could offer any protective effect to the liver. Hyperhomocysteinemia was induced in rats fed a high-methionine diet for 4 weeks. There was a significant increase in the serum aspartate aminotransferase and alanine aminotransferase activities reflecting liver injury in hyperhomocysteinemic rats. Hepatic NAD(P)H oxidase was activated during hyperhomocysteinemia leading to increased superoxide anion production and peroxynitrite formation in the liver. As a consequence, the level of lipid peroxides was significantly elevated in livers of hyperhomocysteinemic rats. Folic acid supplementation effectively inhibited NAD(P)H oxidase-mediated superoxide anion production leading to reduced lipid peroxidation in the liver. Folic acid supplementation also alleviated hyperhomocysteinemia-induced liver injury. These results suggest that hyperhomocysteinemia can cause liver injury and supplementation of folic acid offers a hepatoprotective effect.

Ischemia followed by reperfusion is a major cause for renal injury in both native kidney and renal allografts. Hyperhomocysteinemia, a condition of elevated plasma homocysteine (Hcy) level, is associated with cardiovascular diseases. Recent evidence suggests that Hcy, at higher levels, may be harmful to other organs such as the kidney. In this study, we investigated the role of Hcy in ischemia-reperfusion-induced renal injury. The left kidney of a Sprague-Dawley rat was subjected to either 30-min or 1-h ischemia followed by 1- or 24-h reperfusion. Ischemia-reperfusion caused a significant increase in peroxynitrite formation and lipid peroxidation in kidneys, which reflected oxidative stress. The number of apoptotic cells in those kidneys was also markedly increased. Hcy levels were elevated 2.9- and 1.5-fold in kidneys subjected to ischemia alone or ischemia-reperfusion, respectively. Further investigation revealed that elevation of Hcy level in the kidney upon ischemia-reperfusion was due to reduced activity of cystathionine-β-synthase, a key enzyme in Hcy metabolism. Administration of anti-Hcy antibodies into the kidney not only abolished ischemia-reperfusion-induced oxidative stress and cell death in the kidneys but also restored renal function after 1 h of reperfusion. However, such a protective effect was not sustained after 24 h of reperfusion. In conclusion, ischemia-reperfusion impairs Hcy metabolism in the kidney. Hcy, at elevated levels, is capable of inducing oxidative stress and renal injury. Neutralization of Hcy with antibodies offers transient functional benefit against ischemia-reperfusion-induced oxidative stress and renal injury. These results suggest that Hcy may play a detrimental role in the kidney during ischemia-reperfusion.

Although the herbal cosmetic industry has exponentially increased globally, manufacturing of herbal cosmetic products in Sri Lanka is still very limited. Therefore, objectives of the study were to recognize plants used in commercialized herbal cosmetic products and major constraints faced by herbal cosmetic manufacturers and to identify possible interventions for the development of herbal cosmetic industry of Sri Lanka. Information was gathered via a semistructured questionnaire by personal interviews with 11 large-scale multiple herbal cosmetic products manufacturers. Collected data were analyzed via frequency index for usage and descriptive statistics. A total of 115 plant species belonging to 56 families were identified. Extensive usage of Aloe vera (L.) Burm.f., Coscinium fenestratum (Goetgh.) Colebr., and Santalum album L. (90.91%) was reported among herbal cosmetic manufacturers. The highest number of plants or plant materials was used for manufacturing skin care products (54.78%) followed by hair care (19.13%) and oral care (6.96%). The majority of plants were reported from the plant family Fabaceae (16 species). Leaves (20.87%) were the widely used plant part, whereas 10 plant species were used as whole plants. Inadequacy of 7 plants/plant materials and importation of 8 plant materials for the production were also recognized. As major constraints faced by herbal cosmetic manufacturers, inadequate availability and poor quality of raw materials were emphasized. In conclusion, establishing proper cultivation system, implementing strategies for quality control of raw materials, and conducting ethnobotany, ethnopharmacological surveys to identify cosmetic potential of medicinal plants and partnerships with universities to transfer technology for product development to industries are possible interventions for the development of herbal cosmetic industry of Sri Lanka.

The global consumption of plant-based cosmetics has shown spectacular growth in recent years because of rising consumer awareness regarding the long-term health benefits of natural ingredients. As the global demand for herbal cosmetics increases, there are ample opportunities for Sri Lanka as a tropical Asian country to expand its productions and global exports along with its unique biodiversity and inherited traditional knowledge. Therefore, the present review attempts to give an overview of the widely used medicinal plants in the global herbal cosmetic industry and strengths, challenges, and possible solutions for the development of the herbal cosmetic industry of Sri Lanka. Information was collected using electronic search (using Pub Med, Science Direct, Web of Science, Google Scholar, TEEAL, and Scopus) for articles published in peer-reviewed journals, industrial reports, market surveys, and library search for local books on ethnobotany. Important plant-derived ingredients used in the global herbal cosmetic industry are essential oils, colorants, oils, fats, and waxes. The traditional usage of 108 medicinal plant species (belonging to 58 families) in cosmetic treatments was identified from the local books of Sri Lanka. Of these, 49 plant species were reported as new ingredients for the herbal cosmetic industry. However, the lack of ethnobotanical and ethnopharmacological surveys to identify the cosmetic potential plants, insufficient or absence of continuous supply of raw materials for production in line with the existing demand, the lack of quality control of raw materials and finished cosmetic products, improper systematic cultivation systems for medicinal plants, poor postharvest practices, and the lack of innovations are major challenges encountered in Sri Lanka for the development of the herbal cosmetic industry. In conclusion, addressing these vital knowledge gaps is a timely requirement of the country for the sustainable development of the herbal cosmetic industry in Sri Lanka. Furthermore, assembling of the multidisciplinary cooperation of botanists, chemists, toxicologists, researchers, and biologists is crucial to analyze the interesting functional properties, efficacy, and effectiveness of documented medicinal plants with cosmetic potential.

Medicinal plants have been used for therapeutic and beauty applications in Sri Lanka with documented history of over 2,500 years. This inherited knowledge, which has been handed down from generation to generation, provides a largely unexplored source for the potential development of active ingredients for cosmetic formulations. Therefore, the present comprehensive survey was conducted to identify cosmetic potential medicinal plants species in Sri Lanka. Personal interviews were conducted via a semistructured questionnaire with randomly selected 30 traditional practitioners and 90 Ayurveda physicians in Sri Lanka. Data were collected on plants and specific plant parts used for the treatment of skin care, hair care, and oral care topically. The acquired data were verified using the Ayurveda authentic books and quantitatively analyzed using relative frequency of citation (RFC), use value (UV), relative importance (RI), and factor informant consensus (FIC). Results revealed about the usage of 133 different plant species belonging to 64 families in cosmetic treatments under the categories of skin care, hair care, and oral care. Majority of medicinal plants were used in skin care treatments (39%) followed by hair care (20%) and oral care (17%). Aloe vera (L.) Burm.f. reported the highest RFC value (0.83) and UV (3.66). The highest RI value was reported from Asparagus racemosus Willd. and Hibiscus rosa-sinensis L. (1.67). The dominant plant family was reported as family Fabaceae. The most utilized plant part was stated as leaves (34%) followed by bark (14%). The survey further revealed about treatments for 17 skin-related, 9 hair-related, and 2 oral-related beauty issues. All RFC values were comparatively high for identified different beauty issues. Many herbal preparations were prepared using water as the medium whilst most common mode of application was reported as paste (37%). In conclusion, acquired information could ultimately be utilized for the development of the herbal cosmetic industry through the isolation and characterization of bioactive compounds from the documented plants while preserving the traditional knowledge.

The molecular epidemiology of the virus and mapping helps understand the epidemics' evolution and apply quick control measures. This study provides genomic evidence of multiple SARS-CoV-2 introductions into Sri Lanka and virus evolution during circulation. Whole-genome sequences of four SARS-CoV-2 strains obtained from COVID-19 positive patients reported in Sri Lanka during March 2020 were compared with sequences from Europe, Asia, Africa, Australia, and North America. The phylogenetic analysis revealed that the sequence of the sample of the first local patient collected on 10 th March, who contacted tourists from Italy, was clustered with SARS-CoV-2 strains collected from Italy, Germany, France and Mexico. Subsequently, the sequence of the isolate obtained on 19 th March also clustered in the same group with the samples collected in March and April from Belgium, France, India, and South Africa. The other two strains of SARS-CoV-2 were segregated from the main cluster, and the sample collected from 16 th March clustered with England and the sample collected on 30 th March showed the highest genetic divergent to the isolate of Wuhan, China. Here we report the first molecular epidemiological study conducted on circulating SARS-CoV-2 in Sri Lanka. The finding provides the robustness of molecular epidemiological tools and their application in tracing possible exposure in disease transmission during the pandemic.