Current Role of Dapagliflozin in Clinical Practice.

Dapagliflozin is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors which was approved by USFDA in management of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise to improve glycemic control in adults initially, followed by to reduce the risk of hospitalization for heart failure (HHF) in adults with T2DM and established cardiovascular disease or multiple cardiovascular risk factors. Most recently, it is approved to reduce the risk of cardiovascular death and in adults with heart failure (HF) with reduced ejection fraction (NYHA class II-IV). Dapagliflozin has been studied in a wide range of patients with diabetes and plethora of evidence has confirmed its efficacy as a monotherapy as well as an add-on to the oral therapies and insulin, when compared to placebo. Additional advantages include weight reduction which has been consistently demonstrated in Phase III studies and good tolerability. Also there is a demonstrable reduction in systolic blood pressure in patients treated with SGLT2 inhibitors. DECLARE TIMI 58 study clearly demonstrated that Dapagliflozin was non inferior in reducing major adverse cardiovascular events (MACE) in patients with T2DM and high CV risk compared with placebo. 27% risk reduction in heart failure hospitalisation was noted along without increased risk of amputation. DAPA HF evaluated the efficacy and safety of the dapagliflozin in patients with HF and reduced ejection fraction, irrespective of the presence or absence of diabetes. Patients with symptomatic HF due to reduced ejection fraction treated with dapagliflozin had positive outcomes with reduction in cardiovascular deaths and HF events. The DAPA-CKD trial which was conducted to assess the efficacy and safety of dapagliflozin in patients with chronic kidney disease (CKD), with or without type 2 diabetes found that it significantly lowered the risk of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes in patients with CKD, regardless of the presence or absence of diabetes. Ongoing trials like DELIVER, DAPA ACT HF-TIMI 68, DICTATE-AHF, HF readmission study, DAPA MI Study, Effectiveness of Dapagliflozin for Weight Loss, will throw more light on the precise effects of dapagliflozin in several clinical scenarios. To conclude - Dapagliflozin was well studied not only in T2DM but also in HF and CKD patients with positive results and good safety profile.

Pharmacognostical studies of leaves of Combretum albidum G. Don.

BACKGROUND: Combretum albidum Don belonging to family Combretaceae is an unexplored medicinal plant in the Indian medicinal system. According to ethnobotanical information, the leaves are used in the treatment of peptic ulcer and its fruits are used in diarrhoea and dysentery. Stem bark is used in the treatment of jaundice and skin diseases. The problem encountered in standardisation of this medicinal plant is its identification by source. MATERIALS AND METHODS: The pharmacognostical studies were carried out in terms of organoleptic, macroscopic, microscopic, physicochemical, florescence and phytochemical analysis. Physicochemical parameters such as total ash, moisture content and extractive values are determined by World Health Organization guidelines. The microscopic features of leaf components are observed with Nikon lab photo device with microscopic units. RESULTS: Macroscopically, the leaves are simple, obovate in shape, acuminate apex, entire margin and smooth surface. Microscopically, the leaves showed a large vascular strand that consists of thick walled xylem elements mixed with xylem fibres and phloem which is present in a thin layer along inner and outer portions of xylem. External to the xylem occur a thin line of sclerenchyma. Powder microscopy revealed glandular trichomes in the adaxial epidermal peelings also shows the non-glandular trichomes fairly common in powder and epidermis with anisocytic stomata. Vessels elements are narrow, long, cylindrical and dense multi-seriate bordered pits. Xylem fibres are thin and long, with thick walls, which are lignified. Preliminary phytochemical screening showed the presence of carbohydrate, glycoside, saponin, flavonoid, phytosterols and phenolic compounds. CONCLUSIONS: The results of the study can serve as a valuable source of pharmacognostic information as suitable standards for identification of this plant material in future investigations and applications.

Pharmacognostical evaluation of Cardiospermum halicacabum Linn. leaf and stem.

BACKGROUND: Cardiospermum halicacabum Linn (Sapindaceae) is an important medicinal plant in the traditional system of medicine, known as karnasphota. The root of it is officially included in Ayurvedic Pharmacopoeia for its therapeutic uses such as jvara, kustha, pandu, ksaya and sandhivata etc. As no detailed analysis of macroscopy, microscopy characters of the plant, except root, have been carried out till date, it was thought worth to carry out the detailed macroscopic and microscopic study of leaves and stem, following standard pharmacognostical procedures. MATERIALS AND METHODS: Pharmacognostic studies of C. halicacabum were carried out, and in this, the macroscopic, microscopic, physicochemical, fluorescence and phytochemical analyses were done. Physicochemical parameters such as total ash, moisture content, extractive values were determined by World Health Organization guidelines. The microscopic features of leaf and stem components were observed. RESULTS: Macroscopically the leaves are bi-ternate, ovate-lanceolate in shape with dentate margin. Microscopically, leaf shows prominent midrib and thin dorsiventral lamina. The midrib shows the presence of epidermal layers, angular collenchyma, palisade cells and vascular strands comprised of thin walled xylem and thick walled phloem elements. The lamina shows prominent, narrow and cylindrical upper epidermis. The upper epidermal cells are large and contain mucilage, whereas lower epidermis possesses thin, small and elliptical epidermal cells. The mesophyll was differentiated into two zones upper and lower. The upper zones show narrow cylindrical palisade cells and lower zone shows 2-3 layers of loosely arranged spongy parenchyma cells. In the Paradermal section of the lamina we observe anomocytic stomata. The transverse section of stem shows a pentagonal appearance with five short blunt ridges and prominent cuticle. Parenchymatous cells, cortical sclerenchyma, lignified xylem fibers, phloem and pit were also found. In the powder microscopy of whole plant, glandular trichomes, non-glandular trichomes, fragments of lamina, xylem elements, parenchyma cells and fibers are observed. Phytochemical screening reveals that the C. halicacabum extract contains glycosides, carbohydrates, flavonoids, phytosterols, phenolic compounds and saponin. CONCLUSION: Various pharmacognostic characters observed in this study help in identification, quality, purity and standardization of C. halicacabum.

Pharmacognostical and phytochemical evaluation of the leaves of Ziziphus xylopyrus (Retz) Willd.

BACKGROUND: The fruit decoction of Ziziphus xylopyrus (Retz) Willd. is used toward increase sterility in woman intended birth control in some parts of Rajasthan, India. This plant is widely used in Turkish medicines as a potent sedative. One to two inches of the fresh stem bark of this species are chewed with 1-2 peppers, and the sap swallowed once a day for 5 days in the treatment of cough. Standardization is one of the challenges in herbal medicine. It is essential to evaluate the herbal plants scientifically and proper documentation should be made to know their medicinal properties. MATERIALS AND METHODS: Leaf samples of Z. xylopyrus were studied as recommended by World Health Organization for morphological, microscopic, physicochemical, phytochemical, powder characteristics and other methods for standardization. RESULTS: Morphologically the leaves are obovate or orbicular in shape, pinnate venation having aromatic odour and pungent taste. Microscopically leaves showed the presence of ground tissue, vascular strand, xylem and phloem. The crystals are mostly rosette type. Microscopic examination of powder showed the presence of stomata, covering trichomes, sclerenchyma, collenchyma, epidermal cells and vascular strands. Phytochemical screening of the plant part with various solvents revealed the presence of alkaloids, carbohydrates, steroids and sterol, glycosides, saponins, flavonoids, phenolic compounds, triterpenoids in it. Physicochemical parameters such as ash value extractive values were also determined and results showed that water soluble extractive value to be higher than alcohol soluble extractive value. CONCLUSION: Results may be helpful for further confirmation of selected species and in future these characters may be compared with the new batch of the same plant materials.