Definition
Hypoxis Radix consists of the fresh or dried sliced corm of Hypoxis hemerocallidea Fisch. & C.A. Mey.  (Hypoxidaceae)

Synonyms
H. rooperi S. Moore

Description

Macroscopical

Figure 1a: Live plant

Figure 1b: Corms

Perennial geophyte with a tuberous rootstock; leaves deciduous, in three distinct groups, strap shaped, up to 30cm long × 3.2 cm in width, folded from the midrib, distinctly ribbed, glabrous on the upper surface, softly pilose on the margin and lower surface; flowers (Oct-Jan) yellow, borne on slender villous pedicels; perianth segments ca. 20mm long and 15mm wide, bearing soft hairs on the margin and lower surface; calyx, developing fruit and bracts all villous.

Figure 2: Colour plate from FP5: 172

Microscopical

Figure 3: microscopical features

Characteristic features are: abundant thin walled pale brown cork tissue (3); numerous bundles of calcium oxalate raphides in the parenchyma cells of the central stele, individual needles up to 80μ long (4); the thick walled cells of the central stele containing numerous small round starch grains (1), mostly 7-15μ in diameter with occasional larger grains to 80μ in diameter, with cleft hilum (2); tannin idioblasts with red-brown contents becoming black-green with FeCl_3, in the stele parenchyma (1); the abundant very long thin reticulate vessels, 40-80μ in diameter, staining pink with phloroglucinol/HCl (5).

Crude drug
The corms usually seen in the marketplace are ca. 60mm in diameter but may be up to 25cm in diameter, bearing a ring of stout vertical bristles at the apex and a fringe of numerous secondary roots at the base; brown-black externally, bright yellow internally when freshly cut, darkening rapidly on exposure to air; exudes a sticky resinous yellow juice from the cut surface.

Geographical distribution
Common in grasslands of the Eastern Cape Province, KwaZulu/Natal, Mpumalanga, Northern Province, Gauteng, Swaziland and Lesotho.

Figure 4: distribution map

Quality standards

Identity tests
Thin layer chromatography on silica gel using as solvent a mixture of toluene:diethyl ether:1.75M acetic acid (1:1:1). Reference compound cineole (0,1% in chloroform). Method according to Appendix 2a.

R_f values of major compounds: 0.23 (purple); 0.39 (mustard); 0.47 (purple); 0.78 (pink); cineole: 0.79 (blue-purple)

Figure 5: TLC plate

HPLC on C₁₈ column, method according to Appendix 2b.

Major compounds:
Methanol extract: Retention times (mins): 6.56

Figure 6: HPLC spectrum

Ethanol (70%) soluble extractive value (dried corm): not less than 31.0% (range: 31.07-36.10%)

Purity tests

Assay
Not yet available

Major chemical constituents
A major constituent of the corms of Hypoxis hemerocallidea as well other Hypoxis species is the pentenyne glycoside hypoxoside (figure 7), which on hydrolysis gives an aglycone with the trivial name of rooperol. Up to 4,5% of hypoxoside has been recorded in H. hemerocallidea corms, but the amount appears to vary seasonally¹. The corms are reported to contain, in addition to hypoxoside, β-sitosterol, sterolins (sterol glycosides, up to 9mg/100g) and monoterpene glycosides^2,3. The cytokinins zeatin, zeatin riboside and zeatin glucoside have also been isolated from corms of this species⁴.

Figure 7: chemical constituents

Dosage forms
In traditional medical practice, an aqueous decoction is taken orally; fresh juice from the tuber is applied externally. As a patent remedy, tuber extracts are available in capsule and tablet form.  

Medicinal uses
As traditional remedies, aqueous infusions are given to sickly children as a tonic, and to adults for dizziness and mental disorders, while fresh juice is applied to burn wounds ^{GR1, 12}. Following reports of its efficacy as a remedy for BPH (benign prostatic hyperplasia)⁵., H. hemerocallidea extracts have been used for some years in Europe for this purpose, bioactivity being ascribed to the sterol component. Additional claims, based on hypoxoside activity, have been made for its medical benefits in the treatment of cancer, HIV-AIDS and inflammation⁶.

Note. A general immunomodulatory effect, attributable to phytosterols^{7, 8}, is the basis of efficacy claims for the South African patent remedy, Moducare^®, reputed to be derived from Hypoxis hemerocallidea but in fact manufactured from pine wood extracts. The latter are good sources of β-sitosterol and its glucoside, both of which are common in nature.

Pharmacology/bioactivity
Hypoxoside and its glycone rooperol have been shown to possess antimutagenic and cytotoxic properties ^6. Preliminary tests with hypoxoside indicated low or no toxicity following oral and intraperitoneal administration to mice (LD₅₀ = 0 for 500mg/kg) and intravenous administration to rabbits (>100mg/kg). No foetotoxic or teratogenic effects were noted in mice following oral administration of up to 100mg/kg.

An in vitro/in vivo assessment of antineoplastic activity of Southern African plant species was unable to show cytotoxic activity in cell culture (CA-9KB) of ethanol:water (50:50) fresh leaf extracts, or antitumour activity of similar extracts in mice against Leuk-L1210 and Leuk-P388⁹. In an in vitro/in vivo study of 5-alpha reductase inhibitory activity of a tuber extract, no activity was demonstrated.¹⁰

A clinical assessment of the effects of whole plant extracts of H. hemerocallidea (randomised, placebo-controlled, double blind study involving 200 adult male patients with mild to moderate BPH) reported a statistically significant decrease in symptoms¹¹. Peak flow rate was increased from 9.9 to 15.2 ml/sec and a decreased post void residual volume observed, compared with placebo (dose: 60.0mg/day; duration of trial: 6 months). An 18-month follow-up to the study showed that patients previously randomised to the placebo group, then later treated with the extract, had an improvement both in symptom scores and flow rates. The follow-up also showed that patients who had received Hypoxis extract for the first 6 months of the trial continued to improve during the subsequent 12-month period, irrespective of whether medication was continued or not.

Other clinical studies have demonstrated an improvement in symptoms associated with BPH in patients treated with Hypoxis extracts^{12, 13, 14}.

Whether the efficacy of H. hemerocallidea in the treatment of BPH is due to hypoxoside, sterols or the whole plant extract is not known at present. The efficacy of β-sitosterol in the treatment of BPH is however well-documented ^{5, 15}, as is its immunomodulatory ^7,8 and antimutagenic activity¹⁶.

Contraindications
In view of the sterol content of this species, its use during pregnancy should be undertaken with caution.

Adverse reactions
Taken orally, this species is reputed to cause purging^GR1

Precautions
No special precautions

Dosage
To be determined

References

1. Drewes, S.E., Hall, A.J., Learmonth, R.A. and Upfold, U.J. (1984). Isolation of hypoxoside from Hypoxis rooperi and synthesis of (E)-1,5-bis (3’,4’-dimethoxyphenyl) pent-4-en-1-yne. Phytochemistry 23(6): 1313-1316.
2. Pegel, K.H. (1973). Extraction of phytosterol glycosides from Hypoxis tubers. S.A.Patent ZA 7201855.
3. Wagner, H. and Wiesenauer, M. (1995). Phytotherapie: pp. 198-199. Gustav Fischer Verlag, Stuttgart.
4. Van Staden, J. (1981). Constituents of Hypoxis rooperi, a valuable medicinal plant in South Africa. Deutsche Apotheke Zeitung 33: 460-464.
5. Pegel, K.H. (1984). Β-sitosterol β-D-glucoside (sitosterolin) as the active agent in Harzol^® and other phytopharmaka. Extracta Urologica 1, suppl. 7: 105-111. (In German)
6. Albrecht, C. F. (1996). Hypoxoside as a putative non-toxic, multi-functional prodrug for the treatment of  cancer, HIV-AIDS and inflammatory conditions. Proceedings of the 2^nd IOCD International Symposium, Victoria Falls, Zimbabwe, 25-28 February 1996.
7. Bouic, P.J.D. (1998). Sterols and sterolins-the natural , non-toxic immunomodulators and their role in the control of rheumatoid arthritis. Health Talk 1998: 48-49.
8. Bouic, P.J.D. et al. (1996). Βeta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory vitamin combination. International Journal of Immunopharmacology 18(12): 693-700.
9. Charlson, A.J. (1980). Antineoplastic constituents of some Southern African plants. Journal of Ethnopharmacology 2(4): 323-335.
10. Rhodes, L. et al. (1993). Comparison of finasteride (Proscar), a 5-alpha reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5-alpha reductase inhibition. Prostate 22 (1): 43-51.
11. Lowe, F.C. et al. (1998). A review of recent placebo-controlled trials utilising phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH). Prostate 37(3): 187-193. (Review article)
12. Buck, A.C. (1996). Phytotherapy for the prostate. British Journal of Urology 78(3): 325-336 (Review article).
13. Muller-Christiansen, K. (1993). Besonderer Stellenwert der Phytopharmaka. Therapiewoche 43(26/27): 1490-1496. (German).
14. Dreikorn, K. & Schonhofer, P.S. (1995). The place of phytotherapy in the treatment of Benign Prostatic Hyperplasia. Urologe 34(2): 119-129. (Review article-German)
15. Berges, R.R. et al. (1995). Randomised, placebo-controlled, double blind clinical trial of β-sitosterol in patients with benign prostatic hyperplasia. The Lancet 345 (June 17):1529-1532.
16. Merck & Co. Inc. (1989). The Merck Index 11^th edition, Rahway, Massachusetts.