Does Cat's Claw Raise Testosterone Levels

Does Cat's Claw Raise Testosterone Levels

Rubiaceae

In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016

Uncaria tomentosa

Uncaria tomentosa (cat's claw), an herb from the highlands of the Peruvian Amazon, contains the spiroindole alkaloids isopteropodine and rynchophylline; it has immunomodulatory properties and has been used to treat arthritis and inflammatory bowel disease [11].

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A 59-year-old woman with mantle-cell lymphoma and no hepatic involvement took a range of unconventional medicines [12]. During a routine check-up she had raised liver enzymes, and self-medication with cat's claw was deemed the most likely cause. Cat's claw was withdrawn and her liver tests normalized within 60 days.

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Uncaria tomentosa: A promising source of therapeutic agents for prevention and treatment of oxidative stress and cancer

Francesca Ciani , ... Simona Tafuri , in Cancer (Second Edition), 2021

Abstract

Uncaria tomentosa , called "uña de gato," belonging to the Rubiaceae family, is a thorny liana that grows wild in the upper Amazon region of Peru and neighboring countries. The indigenous people of Amazonian rain forest have used its root/bark over the centuries for the treatment of several diseases, and this plant is believed to have antioxidant, anti-inflammatory, and antitumoral properties.

Many active compounds have been isolated from U. tomentosa, including antioxidants such as tannin, catechins, procyanidins, sterols, triterpenes, flavonoids, carboxyl alkyl esters, and indole and oxindole alkaloids. In particular, alkaloids, the major active components of Uncaria species, have been extensively studied for their potential use as anticancer agents.

In this chapter, some aspects of the actions of U. tomentosa on oxidative stress and cancer have been discussed, after having characterized the plant and mentioned the biochemistry of oxidative stress.

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Solid-State Measurements of Drugs and Drug Formulations

I. Wawer , in NMR Spectroscopy in Pharmaceutical Analysis, 2008

3.3 Oxindole alkaloids from Uncaria tomentosa

Uncaria tomentosa (Cat's claw, Una de Gato, Vilcacora) is a large, woody vine from the Amazon rainforest used medicinally by the native tribes for at least 2000 years. ⁴⁸ Since the early 1990s, cat's claw has been used as an adjunctive treatment for diseases that target the immune system. Its bioactive components include oxindole alkaloids. A series of alkaloids were isolated ⁴⁶ for the purpose of standardization of vilcacora products. Alkaloids may undergo isomerization in solution, therefore solid-state NMR technique was used to characterize the stereoisomers. ^{49 13}C CPMAS NMR spectra for the most abundant alkaloids – mitraphylline (7R,20R), pteropodine or Uncarine C (7R,20S) (Scheme 13), isomitraphylline (7S,20R), and isopteropodine or Uncarine E (7S,20S) (Scheme 14) – were recorded; solid-state chemical shifts are listed in Table 3.

Scheme 13. Alkaloids: mitraphylline (7R,20R), pteropodine (7R,20S).

Scheme 14. Alkaloids: isomitraphylline (7S,20R), isopteropodine (7S,20S).

Table 3. ¹³C CPMAS NMR chemical shifts δ (ppm) for solid alkaloids: mitraphylline, isomitraphylline, pteropodine, and isopteropodine (isolated by Planta Analytica, USA ⁴⁶ )

C	Mitraphylline	Isomitraphylline	Pteropodine	Isopteropodine
	7R, 20R	7S, 20R	7R, 20S	7S, 20S
2	181.7	181.1	182.0	180.9
3∗	74.8	71.5	73.1	71.0/69.9
5	53.0	54.1	54.9	55.4/54.9
6	37.6	35.0	35.6	35.5
7∗	55.1	56.7	56.1	56.9/56.3
8	133.2	134.2	132.8	133.9
9	123.3	124.3	123.1	123.5
10	121.8	122.0	121.5	121.8
11	128.3	127.7	128.5	128.6/128.1/127.6
12	111.5	110.0	111.0	111.9/110.7
13	142.7	141.5	142.8	142.1
14	29.8	30.4	29.7	30.0
15∗	30.5	30.4	31.9	31.8
16	108.0	107.9	110.0	110.7/110.0
17	154.1	154.1	154.1	154.7/154.0
18	15.6	14.9	16.7	18.2/16.7
19∗	74.8	74.0	73.1	72.7
20∗	41.9	41.4	38.3	36.3
21	53.0	53.0	52.1	52.8
22	166.2	166.1	166.3	166.0
23	50.9	50.6	50.1	49.3/48.8/48.6

The resonances can be assigned directly by comparison with the solution data, only solid isopteropodine exhibited polymorphism. The identification of the quaternary carbons was made by means of DD experiments; the standard and DD spectra of pteropodine are illustrated in Figure 6.

Figure 6. ¹³C CPMAS NMR spectra of pteropodine (uncarine C): (a) standard with t _cp  =   2   ms and (b) dipolar dephased.

Mitraphylline and isomitraphylline belong to the normal-type group, which is characterized by the trans relationships of the C/D and D/E ring junctions, the allo-type alkaloids pteropodine and isopteropodine are characterized by C/D trans and D/E cis relationships. In each type of compounds, the stereochemistry can be easily distinguished by solid-state chemical shifts of C3, C15, 1C8, C19, and C20 (Table 3). The 7R stereoisomers at the spiro C7 position are characterized by the C3 signals at δ  =   73.1, 74.8   ppm, whereas in the spectra of 7S the C3 signals appear at δ  =   69.9–71.1   ppm.

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Global Perspective

L.A. Mitscher , in Comprehensive Medicinal Chemistry II, 2007

1.09.23.3 Cat's Claw

Cat's claw (uña de gato) is a tropical vine scientifically named Uncaria tomentosa (Wild.) DC and Uncaria guianensis (Aubl.) (Gmel.) (fam. Ribiaceae), growing primarily in South America, although members of the genus grow in the tropics everywhere. It should not be confused with Asiatic U. gambir (Hunter) Roxb., that is widely used in tanning. Cat's claw has a long folkloric history of use in wound-healing, against cancer, as a contraceptive, and for the treatment of intestinal distress. Many of the putative therapeutic indications appear to be due to the presence of a multitude of pentacyclic oxindole alkaloids. The actions appear to include antioxidant, antiinflammatory, and immunostimulatory actions. A few small clinical trials support this action but fail to be totally convincing. It appears to be without significant toxicity when used in the usual doses. ¹²⁰

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Health Effects of Alkaloids from African Medicinal Plants

Victor Kuete , in Toxicological Survey of African Medicinal Plants, 2014

21.5.4 Isorhynchophylline and Isocorynoxeine

Isorhynchophylline (15) and isocorynoxeine (16), two isorhynchophylline-related alkaloid are oxindole alkaloids found in Uncaria spp. (Rubiaceae) [102,103]. They were identified in Uncaria rhynchophylla (Miq.) Jacks [103], Uncaria tomentosa [104], Uncariae ramulus [105], Uncaria sinensis (Oliv.) Havil. [21]. Compound 16 was extracted from the Egyptian plant Papaver rhoeas (Papaveraceae) [106]. Compound 15 was also identified in the African medicinal plant, Mitragyna inermis (Willd.) O. Kuntze (Rubiaceae) commonly used in traditional medicine to treat malaria [107]. Compound 15 was reported mainly acting on cardiovascular and central nervous system diseases including hypertension, brachycardia, arrhythmia, and sedation, vascular dementia, and amnesia. Compound 15 also had effects on anticoagulation, inhibited vascular smooth muscle cell apoptosis and proliferation, also displayed endotoxemic and antispasmodic activities [102]. Compounds 15 and 16 showed inhibitory effects, similar to that of verapamil, on contractile response to high concentration of potassium ion (rats), CaCl₂ (rats), norepinephrine in normal and Ca²⁺-free medium (rats and rabbits) and ⁴⁵Ca²⁺-uptake (rats) in thoracic aorta with activities two fold lesser than that of verapamil [105]. Compounds 15 and 16 also demonstrated a protective effects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca²⁺ influx [21].

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Osteoarthritis

Dennis Wolff , in xPharm: The Comprehensive Pharmacology Reference, 2007

Experimental Therapies

Agent Name	Discussion
Chondroitin sulfate	Chondroitin sulfate is the most abundant of the proteoglycans in cartilage. It is used as a disease-modifying treatment for osteoarthritis, either by itself or in combination with other nutraceuticals, such as glucosamine. Ingested chondroitin sulfate appears to have measurable bioavailability Volpi (2002) despite its high molecular weight. There is some evidence that it is efficacious in treating osteoarthritis Mazieres et al (2001).
Uncaria tomentosa	Uncaria tomentosa (cat's claw, una de gato) is an herbal medicine marketed as a treatment for osteoarthritis. Limited studies suggest that it may exert some anti-inflammatory/pain-relieving effects Sandoval-Chacon et al (1998), Piscoya et al (2001).
Zingiber officinale	Zingiber officinale (ginger) is marketed as a treatment for osteoarthritis based on historical use. While there may be some minor short-term benefits associated with its use Bliddal et al (2000), Altman and Marcussen (2001).
Diacerein	Diacerein (diacerhein or diacetylrhein) is an anthraquinone found in herbal remedies such as yellow dock (Rumex crispus), a common weed resembling rhubarb. Yellow dock root has been used historically as a cathartic, but was also recommended for arthritis. Diacerein is a precursor for rhein, a substance that may prevent cartilage destruction, perhaps by suppressing the activation of nuclear factor-kappaB Tamura et al (2002), Mendes et al (2002), Pelletier et al (2003).
Vitamin E	Vitamin E is promoted as a treatment of osteoarthritis. Controlled studies have failed to identify any beneficial effects as a treatment for this condition Brand et al (2001).
Niacin	High doses of niacin (vitamin B-3 or nicotinamide) are promoted for the treatment of osteoarthritis Kaufman (1955), Jonas et al (1996).
S-adenosylmethionine (SAMe)	S-adenosylmethonine (SAMe), an endogenous biochemical, is promoted as a nutraceutical for the treatment for osteoarthritis, fibromyalgia, and depression di Padova (1987). Health benefits have also been claimed for cancer, liver diseases, and cardiovascular diseases Poirier et al (2001), Lieber and Packer (2002). The benefits of SAMe may be more easily observed in those with mild osteoarthritis Bradley et al (1994). Because SAMe is relatively difficult to synthesize and chemically unstable it is expensive and there are concerns that various products do not contain the advertised amounts of active ingredient.
Pralnacasan	Pralnacasan is an orally active non-peptide inhibitor of interleukin-1beta converting enzyme. It reduces joint damage in experimental models of osteoarthritis and has been clinical tested as a treatment for rheumatoid arthritis Rudolphi et al (2003). Phase IIb clinical trials were halted (11/03) when high doses were linked to liver failure in an animal toxicology study.
Metalloproteinase inhibitors	Metalloproteinases contribute to cartilage destruction during osteoarthritis and appear to exert a variety of other potentially deleterious effects, such as mediating the release of soluble tumor necrosis factor alpha. Various inhibitors of metalloproteinases are in development Shaw et al (2000), Janusz et al (2002), Aranapakam et al (2003).

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Microbiota and the Urogenital Tract, Pathogenesis, and Therapies

Bryan Tungland , in Human Microbiota in Health and Disease, 2018

14.7.3.2.4.2 Herbal extracts

Certain herbal extracts may also strengthen the immune system. Many herbal extracts interact with medications, and, may as a result, impair or enhance their effects, creating worsening conditions. The following herbal extracts have been shown to be somewhat effective for short term treatment of a UTI or in recurrent UTIs (Cranberry).

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Cranberry (Viccinium macrocapron) standardized to 36 mg PAC type-A linkage (as noted above). Interaction with warfarin, (Coumadin, Jantoven) may inhibit activity of CYP2C9; medications that affect the liver, or aspirin;

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Blueberry (Vaccimium spp.) contains Type A-linkage PACs like cranberry (Head, 2008; Ofek et al., 1991, 1996; Schmidt et al., 2004). Like cranberry, may interaction with warfarin, may inhibit activity of CYP2C9;

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Green tea (Camellia sinensis) standardized decaffeinated extract, 250–500 mg/day, as an antioxidant, antitumor and immunity enhancer (Carbrera et al., 2006);

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Cat's claw ( Uncaria tomentosa ) standardized extract, 20 mg, 3 times/day, as an antioxidant and immune enhancer; DO NOT take Cat's claw if an autoimmune disease or leukemia is present (Heitzman et al., 2005);

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Reishi mushroom (Ganodema lucidum) standardized extract, 150–300 mg, 2–3 times/day, as an immunity enhancer; high dosages may enhance blood-thinning effects of certain medications, such as warfarin (Chan et al., 2005b);

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Milk thistle (Silybum marianum) seed extract (with or without selenium), 80–160 mg, 2–3 times/day, as a liver detoxifying agent, for lower UTI symptoms, and PSA in men; may have estrogen-like properties, and may interact with a wide variety of medications (Vostálová et al., 2013);

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Bearberry leaf (Arctostaphylos uva-ursi) standardized extract, 250–500 mg, 3 times/day, for no more than 4 days as antiseptic with soothing and strengthening properties from hydroquinone (Quintus et al., 2005; Schindler et al., 2002; Türi et al., 1997; Yarnell, 2002). Bearberry leaf has antiadhesive properties similar to cranberry. This herb may interact with lithium used for psychotherapy;

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Cinnamon bark (Cinnamomum verum) contains trans-cinnamaldehyde with antibacterial activity against C. botulinum, S. aureus, E. coli O157:H7, and S. typhimurium (Nelius et al., 2013), and inhibits UPEC biofilm formation on catheters and adhesion and invasion of uroepithelial cells by UPEC (Amalaradjou et al., 2011);

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Indian barberry or tree turmeric (Berberine arisata), Oregon Grape (Mahonia aquifolium), Goldenseal root (Hydrastis canadensis), and Goldenthread (Coptis chinesis) that contain berberine sulfate, an alkaloid in their roots, rhizomes, and stem bark have been shown effective against a variety of microorganisms (Cernakova and Kostalova, 2002; Ettefagh et al., 2011; Head et al., 2008; Scazzacchio et al., 2001; Yarnell, 2002; Zarei et al., 2015).

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CNS, Pain, Metabolic Syndrome, Cardiovascular, Tissue Fibrosis and Urinary Incontinence

T. Biftu , R. SinhaRoy , in Comprehensive Medicinal Chemistry III, 2017

7.14.6.2 DPP-4 Inhibitors From Natural Extracts

Several natural extracts are reported as inhibitors of DPP-4 activity. However, their inhibitory activities are much lower than those of any of the synthetic compounds in clinical development.

Various alcohol, organic, and water extracts of Capsicum annuum, Capsicum in Solanaceae, Rosa gallica, and Uncaria tomentosa are reported to inhibit DPP-4. ²⁷³ A hot water extract of S. chinensis fruits also inhibited human DPP-4 (IC₅₀  =   10.8   ±   1.5   mg   mL^{−   1}). ²⁷⁴

The Castanospermum australe Cunn. seed (CAS) extract gave a DPP-4 IC₅₀ value of 13.96   μg   mL^{−   1}, while the standard used in the assay, diprotin A, had an IC₅₀ value of 1.543   μg   mL^{−   1}. It was also reported that a 150   mg   kg^{−   1} dose of the extract normalizes hyperglycemia in T2DM rats. ²⁷⁵ In addition, 16,17-dihydro-17b-hydroxy isomitraphylline (DHIM), an indole alkaloid isolated from Mitragyna parvifolia, dose-dependently inhibits DPP-4 in vitro (5, 10, and 20   μg of DHIM inhibits 18%, 56%, and 68% of DPP-4 activity, respectively). Diabetic rats treated with DHIM (100   mg   kg^{−   1}) for 8 weeks exhibited markedly reduced plasma glucose concentrations and increased glucose tolerance in response to glucose loading. GLP-1 and IL-10 levels were also significantly increased in treated animals. ²⁷⁵

Grape seed procyanidin extract (GSPE, Vitaceae) inhibits DPP-4 activity in vitro by ∼   70% upon incubation of the enzyme with 200   mg   L^{−   1} GSPE. GSPE also weakly inhibits rat intestinal DPP-4 and plasma DPP-4 activities at the same concentration. ²⁷⁶

Three plants, Pterocarpus marsupium (Leguminosae) (PM), Eugenia jambolana (Myrtaceae) (EJ), and Gymnema sylvestre (Asclepiadaceae) (GS), used in traditional medicine in India, are commonly used for the treatment of hyperglycemia. Their extracts display concentration-dependent inhibition of DPP-4. At an extract concentration of 1000   μg   mL^{−   1}, both PM and EJ exhibited potent inhibitory activity of DPP-4 with IC₅₀ values of 274 and 279   μg   mL^{−   1}, respectively. ²⁷⁷

Anthocyanins (ANC) isolated from blueberry–blackberry wine blends (Ericaceae) were investigated for their DPP-4 inhibitory effects in vitro. ²⁶⁹ ANC fractions strongly inhibited DPP-4 activity (IC₅₀ values ranging from 0.07 to >   300   μM).

Crude extracts of sponge Xestospongia muta and the sea anemones Bunodosoma granulifera and Bartholomea annulata exhibited potent DPP-4 inhibitory activities, with IC₅₀ values of 0.80, 1.20, and 0.138   mg   mL^{−   1}, respectively. ²⁷⁸

Three kinds of traditional Chinese medicine from Xinjiang, Trigonella foenum-graecum L. (Leguminosae) (TF), Cicer arietinum L. (Leguminosae) (CA), and Punica granatum L. (Leguminosae) (PG), inhibited DPP-4 activity with IC₅₀ values of 0.03, 0.09, and 0.19   mg   mL^{−   1}, respectively. ²⁷⁹

The extracts of three traditional Chinese herbs, Hirudo (Annelida), Poria cum Radix Pini (Polyporaceae), and Buddleja officinalis Maxim. (Buddlejaceae), were identified as having DPP-4 inhibitory activity. At a concentration of 300   mg   L^{−   1}, the extent of DPP-4 inhibition by the extracts was 27%, 27%, and 44%, respectively. ²⁸⁰

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Herbal and Over-the-Counter Medicines and the Kidney

Mark S. Segal , Xueqing Yu , in Comprehensive Clinical Nephrology (Fourth Edition), 2010

Acute Kidney Injury

The nephrotoxicity of medicinal herbs most frequently reported in the literature is from countries in southern Africa and Asia. The use of traditional herbal remedies has been implicated in 37.5% of all cases of acute kidney injury in Nigeria. ²⁷ Herbal plants reported as the cause of renal damage include Securidaca longepedunculata (or violet tree), which contains methylsalicylate and saponin; Euphorbia matabelensis, which contains latex; Crotalaria laburnifolia, which contains hepatonephrotoxic alkaloids; Uncaria tomentosa (cat's claw); Lepidium meyenii (common name: maca); Tripterygium wilfordii (lei gong teng); licorice (Glycyrrhiza glabra) root; and Callilepsis laureola (impila). This section describes some of the important examples of nephrotoxicity caused by herbal remedies.

Tripterygium wilfordii Hook F (TWHF) is a kind of Chinese herbal medicine used for 2000 years. It was applied externally for treatment of arthritis and inflammatory tissue swelling for many years. This drug has been found to have immunosuppressive effects that could successfully induce remission of some autoimmune disorders. Its side-effects include gastrointestinal upset, infertility, and suppression of lymphocyte proliferation. A case was reported of a previously healthy young man who developed profuse vomiting and diarrhea, leukopenia, renal failure, profound hypotension, and shock after ingestion of an extract of TWHF. In addition to his hypovolemic shock, he had evidence of cardiac injury by electrocardiography, cardiac enzyme studies, and echocardiography. He died of intractable shock 3 days after the abuse of TWHF. In rats, daily intragastric ingestion of an effective compound extracted from T. wilfordii Hook F for 16 days led to dysfunction of the proximal tubule of the kidney. ²⁸

Cat's claw, or uno de gato, is a Peruvian herbal preparation made from Uncaria, a woody vine found in the Amazon basin. It has been used for various diseases, such as cirrhosis, gastritis, gonorrhea, cancers of the female genital tract, and rheumatism. The oxindole alkaloids from the root bark of cat's claw are thought to invoke its most widely sought-after medicinal effects as an herbal remedy against inflammation. However, it appears that additional unknown substances have an important role in the overall effect of cat's claw extracts. A case of acute interstitial nephritis after the use of this preparation has been reported; renal biopsy showed acute interstitial nephritis, and the renal failure was reversed after withdrawal of the agent. The acute interstitial nephritis is likely to be an idiosyncratic allergic reaction to the remedy. ²⁹

A variety of nephrotoxic mushrooms are confused with edible mushrooms, resulting in acute kidney injury throughout Europe and North America. The Cortinarius species (Cortinarius callisteus, Cortinarius cinnamomeus group, Cortinarius gentilis, Cortinarius orellanus, Cortinarius rainierensis, Cortinarius speciosissimus, Cortinarius splendens, and Cortinarius semisanguineus group) are the most notorious. In North America, the most common mushroom is probably C. gentilis. In 2004, mushroom exposures accounted for 8601 cases and five fatalities, but only three exposures were attributed to the Cortinarius group. ³⁰ However, because more than 80% of mushroom exposures fell into the unknown mushroom category, Cortinarius exposures certainly are higher. ³⁰ Clinically, the history of mushroom ingestion may be remote, particularly with Cortinarius. Although early gastrointestinal symptoms are usually noted at the time of intake, they may not be severe enough for patients to seek medical attention, and symptoms of renal failure may not be manifested until 1 to 3 weeks after exposure. Presentation with a shorter latent period suggests a more severe toxicity and greater risk of severe renal failure than with delayed presentation. Improvement in renal injury may occur within several weeks to months; however, renal injury may last months to years, and patients may require chronic hemodialysis or renal transplantation.

A more recently described mushroom syndrome involves Amanita smithiana/proxima. It is thought that the toxin is 2-amino-4,5-hexadienoic acid. ³¹ Although it causes acute tubular necrosis within hours of ingestion, the clinical outcome is usually good.

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Plant-Derived Immunomodulators

Arathi Nair , ... Bhaskar Saha , in New Look to Phytomedicine, 2019

17.2.1 Low Molecular Weight Bioactive Compounds

A number of low molecular weight compounds have immunomodulatory properties. Alkaloids, heterocyclic compounds containing nitrogen, like Aristolochic acid obtained from the plant Aristolochia clematitis was the first alkaloid found to exhibit immunostimulatory property (Kumar et al., 2012). Aristolochic acid enhanced the phagocytic activity of peritoneal macrophages and leukocytes, but due to its carcinogenic property, its use as an immunostimulant is limited (Hoang et al., 2016). Other bioactive immunostimulatory alkaloids were isolated from Actinidia macrosperma, Cissampelos pareira, Achillea millefolium, and Murraya koenigii. Cepharanthine isolated from Stephania cepharantha and Vincristine from Catharanthus roseus is found to stimulate the production of antibodies (Yamanoi et al., 2017). Cepharanthine also counteracts the effect of cytostatic agents on hematopoiesis (Seubwai et al., 2010). Small molecular weight compounds such as Vincristine (Jantan et al., 2015) and Staurosporine exhibit immunomodulation in a dose-dependent manner, lower doses acting as an immunostimulant while higher doses as an immunosuppressor. Alkaloids isolated from Uncaria tomentosa increased the number of granulocytes (Farias et al., 2011). A beta-carboline indole alkaloid harmine, isolated from Ophiorrhiza nicobarica, inhibit lysine-specific demethylase-1 during immediate early transcription of herpes simplex virus 1 and 2 in vitro and in infected animal. The interference on early transcription, a decisive factor for HSV lytic cycle or latency, reveals an epigenetic target that may help to develop a nonnucleotide antiherpesvirus drug (Bag et al., 2013, 2014). Thiosulfinate obtained from Allium hirtifolium are potent adaptogens and immunomodulators (Jafarian et al., 2010). Naphthoquinones also showed similar effects on lymphocytes and granulocytes (Wagner et al., 1988). Plumbagin, a quinoid compound isolated from the roots of Plumbago zeylanica, was found to inhibit the growth of hormone refractory prostate cancers (Hafeez et al., 2015) and limits the growth of Staphylococcus aureus (Nair et al., 2016). Terpenes and its oxygenated derivatives terpenoids, for example, Amyrine from Bauhinia variegata (Nadkarni and Nadkarni, 1954), Eugenol from Ocimum sanctum (Vaghasiya et al., 2010), diterpene from Andrographis paniculata, Achillea millefolium, Alternanthera tenella and pentacyclic triterpene from Cecropia telenitida act as immunomodulators (Peláez et al., 2013). The sapogenins triterpenoids and diterpenoids from Gymnema sylvestre have diverse immunomodulatory potentials. Immunostimulatory phorbol esters (derivatives of tetracyclic diterpenoids phorbol) are anticancer drugs at lower doses (Goel et al., 2007). Cichoric acid isolated from Echinacea purpurea activated phagocytic cells both in vitro and in vivo (Manayi et al., 2015).

Plant-derived glycosidase are organic sugar ethers that yield sugar on acid or enzymatic hydrolysis. These include iridoid glycosides of Picrorhiza scrophulariiflora and anthraquinone glycosides of Andrographis paniculata. The Chinese medicinal plant Dendrobium nobile yields sesquiterpene glycosides Dendroside A, Dendronobilosides A and B that exerts proliferative effects on lymphocytes. Flavonoids are another class of phytocompounds that exerts immunomodulatory effects. Lasure et al. (1994) reported the effect of flavonoids on the activation of complements using hemolytic assay and found that quercetin, quercitrin, rutin, myricetin, taxifolin, pelargonidin chloride, and cyanidin chloride inhibited the classical pathway, while hyperoside, myricetin, baicalein, and pelargonidin chloride inhibited the alternative pathway in a dose-dependent manner. Other flavonoids like apigenin, anthocyanidins (Bhattacharya and Muruganandam, 2003), flavones, isoflavonoids, and oligomeric proanthocyanidins (Davis and Kuttan, 2000) found in plants like Terminalia arjuna show immunomodulatory potential. In addition to this phenolic compounds isolated from Euphorbiaceae family also inhibit the classical pathway of complement activation. Coumarin glycosides isolated from Achillea millefolium, Citrus natsudaidai, and Heracleum persicum revealed immunomodulatory properties. Hydroxycoumarins like Esculin, Esculetin, and Scopoletin enhance complement-mediated hemolysis. Esculentin a class of 6,7-dihydroxycoumarin isolated from Euphorbia lathyris, Citrus limonia, and Artemisia capillaris have been attributed with a wide range of immunomodulatory properties (Leung et al., 2005) like free radical scavenging, protecting DNA against oxidative damage. It also shows cancer chemopreventive, antitumor, lipoxygenase-inhibitory activity, and tyrosinase-inhibitory activity. Certain plants and plant-derived compounds like polysaccharides and lipopolysaccharides can activate the alternative pathway of complement activation and hence play a key role in the regulation of inflammation. Moreover, plants like Rosmarinus officinalis L. containing the bioactive component Rosmarinic acid can inhibit the complement system via blocking both the classical and alternative pathways of complement activation (Sahu et al., 1999) (Fig. 17.5).

Figure 17.5. Structure of common low molecular weight immunomodulatory compounds.

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Does Cat's Claw Raise Testosterone Levels

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