Citrus hystrix C hystrix DC commonly known

Citrus hystrix (C. hystrix) DC (commonly known as Kaffir lime) and Citrus maxima (C. maxima) L are giant citrus (commonly known as Pummelo) originated from South East Asia, India and cultivated throughout the tropical and temperate regions for the fruits. C. hystrix is pear-shaped, bumpy, greenish yellow fruit with acidic flavor with very thorny bush, aromatic leaves and fruits. The leaves are strongly aromatic, one or two fresh leaves can be torn, chopped and used as a spice and for various flavoring purpose in Southeast Asian and Thai dishes. Also, small pieces of fresh leaves are added with butter milk to prevent the peroxidation of lipids due to the presence of associated bioactive compounds i.e. polyphenols and enhance the digestive system of stomach. It is used as traditional medicine for headache, flu, fever, sore throats, bad breath and indigestion [6]. The regular use of rubbing fresh leaves on the teeth and gum could aid in dental health. Many active compounds were isolated from leaves of this plant such as phenolic acids, flavonoids, limonoids, coumarins, glycerolipids and α-tocopherol. They possess various pharmaceutical effects such as anti-tumor, antimicrobial, anti-inflammation and antioxidant activities [7–11]. C. maxima fruit is the largest of all citrus variety. It is globose, pear-shaped with 11–14 segments. The pulp appears as white or pinkish red with spindle-shaped juice sacks that separate easily from one another and sweetish-acidic flavor. The leaves are large 5–10cm×2–5cm long size, ovate to elliptical shape, frequently emarginated, obtusely acute apex and dotted glandular [12]. Traditionally leaves are used in the treatment of convulsive cough, cholera, epilepsy and hemorrhagic diseases. Leaves possess the important classes of phytochemicals such as alkaloids, saponins and FHPI [13]. The major essential oils such as DL-limonene, E-citral, 1-hexene-4-methyl and Z-citral were analyzed through GC–MS in the leaves and they exhibit antifungal, antiaflatoxigenic and antioxidant activity [14]. The leaves exhibit a variety of pharmaceutical effects such as antioxidant, hepatoprotection, anticancer, antimicrobial, antihyperglycemic, antidepressant, anti-inflammation and analgesic activity [15–19]. Hence, the aim of the present study was to investigate and compare the hepatoprotective effects of crude methanolic extracts of C. hystrix and C. maxima (Red and White) leaves on paracetamol induced acute liver toxicity in rats. The protective effects were compared with silymarin, a well known hepatoprotective agent against paracetamol induced hepatotoxicity.
Materials and methods
Results
Discussion Plant medicines play an important role by their various formulations for the treatment of various diseases. Some have been analyzed and scientifically validated for their potentials. Here, we designed the experiments to examine the hepatoprotective activity of methanolic extract of leaves from underutilized C. hystrix and C. maxima (Red and White) for their development into safe natural drug candidates. Paracetamol (acetaminophen) is widely consumed as an antipyretic drug that is safe in therapeutic doses but can cause fatal hepatic damage in human and animal at higher toxic doses. Bioactivation of paracetamol by hepatic cytochrome P-450 leads to formation of a highly reactive and toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is normally detoxified by conjugation with reduced glutathione (GSH) to form mercapturic acid which is excreted in urine. Toxic overdose of paracetamol depletes hepatic GSH content so that free NAPQI binds covalently to cellular mitochondrial proteins which suppresses mitochondrial fatty acid β-oxidation and results in massive necrosis and apoptosis of hepatocytes [27,28]. An obvious sign of hepatic injury is the leaking of cellular enzymes such as ALT, AST and ALP into plasma due to the disturbance caused in the transport functions of hepatocytes. ALT is more specific to the liver, and it is a better parameter for analyzing hepatic injury. High levels of AST indicate the cellular leakage as well as loss of functional ability of cell membrane in liver. Serum ALP is also related with liver cell damage. High concentration of ALP cause serious hepatic damage in paracetamol treated rats [29]. Liver is the major source of most of the serum proteins. Bilirubin is a product of heme within the reticuloendothelia system; its elevation in the blood stream can be adduced to over production, increased hemolysis, decreased conjugation or impaired bilirubin transport [30]. Bilirubin is an index that is used to assess the normal functioning of the liver instead of the extent of hepatocellular injury.