Phytochemistry of Plants of Genus Cassia by Brijesh Kumar;Vikas Bajpai;Vikaskumar Gond;Subhashis Pal;Naibedya Chattopadhyay;

Author:Brijesh Kumar;Vikas Bajpai;Vikaskumar Gond;Subhashis Pal;Naibedya Chattopadhyay; [Kumar, Brijesh]
Language: eng
Format: epub
Tags: HEALTH & FITNESS/Herbal Medications, MEDICAL/Pharmacology, SCIENCE/Chemistry/General
ISBN: 9781000458091
Publisher: CRC Press (Unlimited)
Published: 2022-09-15T00:00:00+00:00

4.3 The Effects of CO Extract Fraction and Formulation

Since the nineteenth century, extracts of leaf and stem were used for accelerated fracture healing as a traditional medicine in Puttur (Andhra Pradesh, India) (Singh, 2017; Yadav et al., 2010). Pal et al. showed that ethanolic extracts of stem and leaf were effective for bone regeneration at fracture site in a femur osteotomy model. The stem extract of CO (CSE) was effective at 250 mg/kg versus 750 mg/kg dose of the leaf extract of CO (CLE) (Pal et al., 2019). From the butanolic fraction of CSE, ten compounds were isolated out of which six were found to be osteogenic through in vitro assessments of ALP activity and expression of osteogenic genes that included bone morphogenetic protein-2 (BMP-2), runt-related transcription factor-2 (Runx2) and type 1 collagen (col1). The osteogenic compounds were apigenin, luteolin, emodin, isovitexin, 4′,7′-dihydroxyflavone and 3′,4′,7′-trihydroxyflavone (Pal et al., 2019). Among the osteogenic compounds, isovitexin and 3′,4′,7′-trihydroxyflavone were found to upregulate all three osteogenic genes thus suggesting these two compounds to be more effective than the other four in stimulating bone formation. The butanolic fraction of CSE (CBE) increased bone regeneration in the femur osteotomy model at 100 mg/kg dose, which suggested enhancement of the osteogenic activity of CBE over CSE which was attributed by the enrichment in CBE of six osteogenic compounds described before (Pal et al., 2019).

In a widely used model of iatrogenic osteoporosis obtained by the administration of a corticosteroid, methylprednisolone (MP), CSE (250 mg/kg) and CBE (100 mg/kg) mitigated MP-induced bone loss and strength by osteogenic as well as anti-catabolic actions. Even at a 2.5-fold lesser dose than CSE, the osteogenic effect of CBE was significantly greater than CSE. Both CSE and CBE mitigated MP-induced loss of body weight and electrolyte imbalances with later being more effective (Pal et al., 2019). Through an LC-MS/MS method, apigenin, isovitexin, luteolin, emodin and trihydroxyflavone were detected in adult rat plasma after an oral administration of CSE (500 mg/kg) (Pal et al., 2019). These compounds were stable in simulated gastric and intestinal fluids but were metabolized in rat liver microsomes. The development of bioanalytical methods for pharmacokinetics and in vitro stability studies of osteogenic compounds will be useful for the phase 1 clinical trial.

Self-nano emulsifying drug delivery system (SEDDS) is an efficient mode for improving the bioavailability of poorly absorbed compounds often present in phytoextracts. A lipid-based SEDDS of CBE was found to enhance the bioavailabilities of apigenin, isovitexin, THF, luteolin and emodin along with the increase in the skeletal effect. However, CBE at 100 mg/kg dose increased osteogenic effect, the SEDDS formulated CBE achieved the same effect at 50 mg/kg (Pal et al., 2020). The study also found that MP treatment significantly suppressed osteocyte markers including dentin matrix acidic phosphoprotein 1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE), and SEDDS formulated CBE maintained their expression (Pal et al., 2020). Muscle atrophy is another signature of GC treatment and we found that SEDDS-formulated CBE significantly improved muscle structure and prevented muscle atrophy.

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