Agriculture Reference
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interferon gamma (IFN-γ), and TNF-α was enhanced without growth inhibition. In addition, cyto-
toxicity of activated PBMCs against K562 was enhanced by the addition of CP extract. Moreover,
microarray analyses showed that the expression of 23 immunomodulatory genes, classified by
gene ontology analysis, was enhanced by the addition of CP extract. In this regard, CCL2, CCL7,
CCL8, and SERPIN B2 were representative of these upregulated genes and thus may serve as
index markers of the immunomodulatory effects of CP extract. It is interesting to note that the
identified active components of CP extract, which inhibited tumor cell growth and stimulated
antitumor effects, have a molecular weight of less than 1000. It has been suggested that the CP
leaf extract may potentially provide the means for the treatment and prevention of selected human
diseases, such as cancer and various allergic disorders, and may also serve as a immunoadjuvant
for vaccine therapy. 372
The methanolic extract of the seeds showed male contraceptive activity in laboratory animals. 372
Treatment at various dose regimens daily for 52 weeks did not show significant changes in body
weight, organ weight, food and water intake, or preterminal deaths compared to those of control
animals. Sperm count and viability in animals treated with 50 mg/kg body weight and the weight
of epididymis, seminal vesicle, and prostate of all the treated animals showed significant reduction
compared to a control. Cauda epididymal spermatozoa of animals treated with 50 mg/kg body
weight were immotile. Azoospermia was observed at various doses in the treated animals. Serum
clinical parameters, serum testosterone, and histopathology of vital organs were comparable to
those of control animals. It was also reported that the histology of testes revealed adverse effects on
the process of spermatogenesis, while the histology of the epididymis, seminal vesicles, and ventral
prostate showed no changes compared to the control. 373
Clinical Applications — The proteolytic enzymes are listed in most pharmacopoeia and are
incorporated into proprietary products for digestive disorders. Papain has been given as enteric-
coated tablets in a dose of 1.98 g with every meal to reverse a malabsorption syndrome that was
incompletely controlled by gluten-free diet and considered to be due to transient gluten intoler-
ance. 374 The enzyme is dispensed as an antitoxic agent for diphtheria and tetanus and is used exter-
nally for the healing of wound sores. A 4% w/v solution of the homogenized fruit pulp and 1% boric
acid has been found effective in the healing of tropical sores. 313,314 Chymopapain is employed in the
treatment of herniated disks by chymonucleolysis. Reviews of the use of chymopapain in the repair
of disk disorders are available. 375,376
The alkaloids have broad-spectrum antimicrobial activity. Carpaine inhibits the tuberculosis
bacteria, Mycobacterium tuberculosis , but in high doses possesses a digitalis-like action that may
cause cardiac paralysis and depression. In small doses (0.01-0.02 mg/day p.o. or 0.006-0.01 mg/day
s.c.), carpaine hydrochloride was found useful in hypertension. 377 Tropaoline is bactericidal and
has been indicated for intestinal and injury infections. 368 Xylitol possesses antihemolytic activity
and has been reported to lower bilirubin levels in rats intoxicated with parenteral administration
of saponins. 378 A paste made from the leaves of pawpaw, mixed with opium and sodium chloride,
applied for 3 days was helpful in the relief of symptoms and easy extraction of guinea worm from
the body. 379 The leaf extract is also effective against dengue fever. 373
Toxicity — Allergic reactions to papaya appear to be common. 380 Rhinitis, asthma, and other
allergic reactions are sometimes experienced by health professionals handling papain-containing
powders. 367 A major adverse reaction associated with chymopapain is anaphylaxis, which can occur
in up to 1% of patients. 381 Papaya, in addition to glucosinolates, contains low levels of cyanogenic
glycosides (CNGs), an unusual occurrence because it was assumed that the two classes of metabo-
lites were mutually exclusive. It is suggested that CNGs may be responsible for the antibiotic effects
of the seeds and the laxative effect of the immature fruit. The accumulation of CNGs in the latex
and leaves of papaya, although currently detected in edible parts at very low levels, may have poten-
tial human health implications. 382
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