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Revista Brasileira de Farmacognosia

Print version ISSN 0102-695X

Rev. bras. farmacogn. vol.25 no.1 Curitiba Jan./Feb. 2015

http://dx.doi.org/10.1016/j.bjp.2014.11.011 

Original Articles

Aspidosperma subincanum II. Usefulness of uleine and ribonucleic fragments in the treatment of AIDS patients

Dominique Maes1 

Roland Maes1  * 

1Parabolic biologicals, Beauvechain, Belgium

ABSTRACT

Aids patients were treated during a year with three different food supplements commercially available: para-pau-aspido (Aspidosperma subincanum Mart. ex A. DC., Apocynaceae); 2Leid (nucleic acids and cytokines); and Para Immuno (propolis, pollen and royal jelly). All foods, given either alone or in combination, proved useful to all AIDS patients who received the supplements, be these under tri-therapy (Triomine: stavudine, lamivudine, névirapine) or left unattended.

Key words: Uleine; HIV; Tri-therapy; Ribonucleic Acid Oligomers (RNO)

Introduction

The treatment of AIDS patients rests on the administration of three chemicals designed to reduce the viral load. The HIV is immunodepressive but no effort is made during chemical treatment to stimulate the multiplication and activity of lymphocytes. This stimulation would however benefit the patients because some drugs are known to be immunosuppressive, which add to the immunodepression induced by the pathogen. Means exist to stimulate the immune response, either by inducing the synthesis of nitric oxide by lymphocytes and other cells, or else by promoting the multiplication of lymphocytes.

Uleine (1), present in Himatanthus lancifolius and Aspidosperma subincanum Mart. ex A. DC., Apocynaceae, have been extensively studied (Seidl et al., 2010). Its capacity to promote the synthesis of nitric oxide (Souza et al., 2007) makes of these plants candidates for use as an adjuvant in the treatment of patients suffering from an immune-depression. The bark of Aspidosperma subincanum has been purified and the food supplement rich in uleine so obtained has been demonstrated innocuous (Federlin et al., 2014).

Nucleic acid oligomers have been shown to inhibit in vivo Shope fibroma and vaccinia viruses (Beljanski et al., 1975). This effect was traced to a stimulation of the multiplication of lymphocytes and platelets (Beljanski and Plawecki, 1979). Lymphocyte populations depleted in vivo by cyclophosphamide responded to a stimulus of ribo-oligo-nucleotides (Beljanski et al., 1983). This positive effect of regeneration of lymphocytes by nucleic acids observed in vivowas verified on two malignant lymphoma cases (Donadio et al., 1991).

These food supplements would appear useful to help the immune system of immuno depressed patients as tuberculosis and Aids patients to counter the immunodepressive activity of the pathogens as well as the immunodepressive activity of some drugs used to eliminate the pathogen. This hypothesis was verified by administering the supplements during a year to AIDS patients. In addition, a third food supplement consisting of propolis, royal jelly and pollen, known to stimulate the immune system, was also offered to the clinician, enabling her to make a complete study of available immuno stimulators.

The clinician focused on the improvement of the health of her patients by verifying the activity of a combination of food supplements given to patients either under chemical treatment or else, due to lack of resources, left unattended. Lack of resources restricted the monitoring in the course of time of the effects of the treatments, to weight and lymphocyte numbers.

The detailed raw results (66 pages) are available (Bouillon and Ndayikunda, 2006). The authors analysed and exploited them.

Materials and Methods

Uleine source and the immunostimulant

Uleine (1) was extracted from the plant Aspidosperma subincanum Mart. ex A. DC., Apocynaceae, and presented as the food supplement “Para-pau-aspido” by the Company Parabolic Biologicals (Beauvechain, Belgium) under two different concentrations: PP20 (20 mg total alkaloids) and PP 80 (80 mg total alkaloids). A supply of the products sufficient to cover a year of treatment was donated. The food supplement “Para Immuno” elaborated by the Company Parabolic biologicals was made of propolis extracted from bee-hives, Royal Jelly and pollen. This product was donated in amounts sufficient to cover a year of treatment.

2Leid is prepared by the laboratory “Laboratoire Labo-Life”. This immunostimulant to be taken sub-lingually is made of cytokines, ribonucleic acids, deoxyribonucleic acids and TGFbeta, and the product was donated in amounts sufficient to cover a year of treatment.

Triomine 530: stavudine 30 mg, lamivudine 150 mg, névirapine 20 mg, for patients whose weights was inferior to 60 kg.

Triomine 540: stavudine 40 mg, lamivudine 150 mg, névirapine 200 mg, for weights over 60 kg.

Clinical studies

Number of subjects treated was eighty, of whom sixty were included in this study. They were orphans at the orphanage “Maison Shalom”, located in the Burundi.

The files of the patients were a year old when the study was initiated in 2006 and many showed an unfavourable clinical symptomatology and opportunist infections, i.e. chronic diarrhoea, persistent fever, generalised lymphadenopathies, diverse pneumopathies, mycoses, generalised dermatoses, zona, alteration of the general state, loss of weight and asthenia. Nearly all patients had conserved their symptomatology when the treatment with supplements started and some had worsened and developed additional opportunist infections.

Among the subjects under tri-therapy since six months, some showed no clinical change, others had developed new opportunist illnesses and others were intolerant to the tri-therapy. Those patients under tri-therapy who showed no improvement and who had developed opportunistic infections that were not observed before the chemical treatment, were included in the study.

CD4’ were monitored at time one year before treatment (T-1) and at the initiation of the treatment (T0) but this monitoring could not be pursued. Weight and total lymphocyte numbers were monitored one year before treatment (T-1), at time 0 (T0), 3 months (T3) and 12 months (T12) after initiation of food supplement treatment. Treatment was stopped at T12.

The food supplement was approved by the Belgian Ministry of Health on June 23 2009 and does not require the approval of an Ethics committee for its use.

Results

Table 1 presents results of fourteen patients who were under conventional tri-therapy for about six months before addition of the food supplements to the treatment. Their state of illness was advanced. The regimen was given according to the medical imperatives defined by the treating physician. Three very ill patients under tri-therapy who died either at the beginning of the treatment or within the first three months of treatment were omitted because treatment with food supplements is a long-term process that could not have been effective at their stage of the illness. Table 2 shows the results of 46 AIDS people who were without specific medical treatment. Their state of illness was less severe than the patients under tri-therapy. The results obtained by patients under tri-therapy are presented at some length because these results are most interesting.

Table 1 Fourteen AIDS patients under conventional tri-therapy. These patients were advanced in disease, with only #9 and #10 in a conserved state. For this reason, they were chemically-treated but the treatment sometimes worsened their condition, shown by a loss in weight (e.g. #2, 11, and 14, or else a status quo: e.g. #5, #6, #10). Some underwent a severe loss of CD4 during the treatment: e.g. #6, #7, #11, #12). All gained in lymphocytes numbers during food supplement treatment. 

  Patient   Treatment   Symptoms Weight Viral L CD4   Lymphocytes
File Age Sex   PP 2Leid P.I.   T0 T-1 T0 T3 T12 T-1 T-1 T0   T0 T3 T12
1 LB 42 19 F   80 yes yes   3, 5, 16, 17   30 45 51     6   212 2915 3600
2 LA02 26 F   80 yes yes   3,6,5 55 50 62 69 120000 84 80   131 2760  
3 LA49 34 F   80 yes yes   very bad 46 51 62 70 125000 25 24   802 2615  
4 LA50 36 F   80 yes yes   very bad 56 62 72 83 125000 62 56   904 2464  
5 LA18 20 F   80 yes     3,4, very bad 44 45 60 80 140000 34 2   151 1768 2916
6 LB41 20 M   80 yes     3,4, very bad 60 60 61 66 0 611 90   402 1915 2690
7 LA32 32 F   80 yes     3,4, very bad 44 46 56 60 98650 245 40   806 2900 3050
8 LA35 37 F   80 yes     3,4, very bad 47 55 72 79 150000 16 127   679 2464  
9 LB33 12 F   80       Conserved   30 32 53     191   720 1920 4500
10 La15 21 F   80       conserved state 59 60 65 76 20000 200 204   1504 2115 3915
11 LA06 30 F   80       2,3, 5, 6 46 40 53 67 120000 95 59   300 1584 3900
12 LA23 31 F   80       3, 13,6,5, 55 50 66 75 135000 50 60   800 2160 3916
13 LA31 15 F   20   yes   3, 6, 5 24 26 33 40 0 435 100   802 2005 3050
14 LA07 23 F     yes     6, 3, 11 45 40 52 64 10 000 300     1401 2500 3900

Viral L: viral load.Treatments: PP: para aspido, 20 or 80 units; 2Leid: cytokines and nucleic acids; PI: royal jelly, propolis, pollen. Tritherapy: stavudine, lamivudine, nevirapine. Symptoms: 1. congenital; 2. adenopathy; 3. diarrhea; 4. dermatitis; 5. pneumopathy; 6. hyperthermy; 7. Inappetence; 8. shingles; 9. otitis; 10. pharyngitis; 11. coughing; 12. psychomotor delay; 13. lymphadenopathy; 14. candidiasis; 15. vomiting; 16. hepatitis; 17. sarcoma

Table 2 46 patients receiving no standard chemical therapy. Some patients were with opportunistic diseases but a sizable number were in good state or "conserved". All of them saw the number of their lymphocytes increase during treatment. 

  Patient   Treatment Symptoms Weight Viral L. CD4   lymphocytes
File Age Sex   P.P. 2Leid P.I. T0 T-1 T0 T3 T12 T-1 T-1 T0   T0 T3 T12
15 LB52 15 F   80 yes yes 3, 6, bad 45 30 35 45 0 610     924 1802 2720
16 LC03 17 F   80 yes yes conserved   44 54 60         1121 3915  
17 LB64 19 F   80 yes yes conserved   58 69 73         1215 2280  
18 LB60 20 F   80 yes yes good state 59 50 60 65 0 488     1320 3916 4200
19 LA21 23 F   80 yes yes good state 51 54 60 66 75000 95 420   1420 2850 3915
20 LA36 31 F   80 yes yes good state 60 65 73 81 0 500 318   1412 4080  
21 LC02 35 F   80 yes yes 3,6, 14, bad   40 42 76         902    
22 LB23 20 F   80 yes   conserved 60 65 70 74 6000 296 315   1390 2500 3920
23 LA20 21 F   80 yes   +/-' good 48 52 58 64 122000 50 105   1240 1539 2620
24 LA39 35 F   80 yes   conserved 40 45 65 75 120000 25 312   1219 2900 3620
25 LC04   M   80 yes   3, 6, 17   50 60 65         502 2108  
26 LB30 20 F   80     conserved 35 50 61 66 10000 205 310   1311 2530 3910
27 LB19 20 F   80     good state 60 65 66 75 0 391 320   1301 1320 3900
28 LA33 30 F   80     conserved 46 50 60 65 100050 250 360   1250 2500 3200
29 LA13 3 F   20 yes yes 3, 6, 5, 12 6 7 12 18 130 000 80 60   1201 2100 4610
30 LA45 3 F   20 yes yes good state 7 12 17 23 125000 25 391   1210 4608 5105
31 LA26 9 M   20 yes yes good state 14 16 20 36 0 420 402   1240 2100 4112
32 LA08 10 F   20 yes yes 6, 3, 7, 4, 9 21 21 30 46 6 000 300 277   1314 3915 4904
33 LA44 10 F   20 yes yes good state 14 20 30 37 125000 85 420   1311 3016 3620
34 LA05 12 F   20 yes yes 1, 6, 3, 8 28 29 35 51 12 000 250 277   1360 3005 4915
35 LA09 12 F   20 yes yes 1, 9, 4 25 25 38 45 0 350 244   1901 2615 3916
36 LB53 13 M   20 yes yes very bad   13 20 25         612 3360 4600
37 LA04 14 F   20 yes yes 5, 8 31 28 35 43 .50.000 140 130   1211 2900 4190
38 LA40 14 F   20 yes yes good state 16 20 30 46 53500 250 305   1229 3050 4215
39 LA01 11 M   20   yes 2,3, 4, 5, 10 26 24 30 35 80 500 120 100   711 2110  
40 LB46 21 F   20   yes conserved   59 65 75     226   1247 3024 4500
41 LA27 4 M   20 yes   good 11 11 15 21 0 500 305   1321 1910 2915
43 LA41 10 M   20 yes   good 16 20 26 40 25000 350 315   1319 3600 4250
44 LA17 11 M   20 yes   +/-' good 15 20 25 35 130000 100 60   405 1120 2905
45 LA30 13 M   20 yes   conserved 19 21 31 36 0 600 372   1120 2820 3912
46 LA03 15 F   20 yes   3,7 45 41 50 60 110 000 91 300   1707 2910 4210
47 LA43 9 F   20     good 13 20 25 36 15000 350 416   1620 2600 3950
48 LA29 11 M   20     conserved 24 25 30 36 0 480 450   1200 2912 4045
49 LB35 12 F   20     conserved 19 22 29 35 0 412 383   827 1460 2920
50 LB32 13 F   20     Conserved 30 32 40 45 5000 490 259   561 1768 2900
51 LB13 19 M   20     good state 60 62 75 79 0 526 620   1302 4901  
52 LA10 21 F     yes yes   60 55 61 72 30 000 200     1500 2500 4600
53 LB04 3 F     yes   3 12 12 15 26 0 710     1400 3500  
54 LB02 4 F     yes   3,6, delayed growth 12 13 18 24 0 420     1830 2930  
55 LB17 5 F     yes   3, 15, 14 18 18 25 30 0 518     1150 3900 4600
56 LB08 7 F     yes   6,14 18 18 25 37 0 520     1200 4500  
57 LB21 21 F     yes   3, 6, 7 60 42 45 50 0 620     1950 2500 3600
58 LA25 25 F     yes   3,4,14 44 45 60 65 10000 360     1300 3900 4115
59 LA22 26       yes   conserved state 55 50 61 67 8000 300     1200 2700 4105
60 LA47 33 F     yes   3, 6, 5 tuberc. 52 51 61 71 5500 350     1250 2950 3920
  LA38 33 M     yes   conserved state 46 46 55 66 60000 300     1220 2915 2400

Viral L: viral load. Treatments: PP: para aspido, 20 or 80 units; 2Leid: cytokines and nucleic acids; PI: royal jelly, propolis, pollen. Tritherapy: stavudine, lamivudine, nevirapine Symptoms: 1. congenital; 2. adenopathy; 3. diarrhea; 4. dermatitis; 5. pneumopathy; 6. hyperthermy; 7. Inappetence; 8. shingles; 9. otitis; 10. pharyngitis; 11. coughing; 12. psychomotor delay; 13. lymphadenopathy; 14. candidiasis; 15. vomiting; 16. hepatitis; 17. sarcoma.

Patients under tri-therapy

P.P 80, 2Leid and P.I. and tri-therapy

The first four patients (Nbs. 1 to 4) were in a critical physical condition at time zero (T0) and received the combination [P.P 80 + 2Leid + P.I. + tri-therapy]. Patient 1 was a 19-year old girl. She weighed 30 kg at the beginning of the treatment (T0) and the number of CD4 cells had collapsed down to 6. Evidently, she did not benefit from the tri-therapy and seemed doomed. In three months of food supplements intake (T3), she gained 15 kg and her number of total lymphocytes increased from 212 to 2915. She was in good health at T12, after 12 months of the additional alternative treatment.

The tri-therapy followed from time T-1 to T0 appeared more beneficial to patients 2 to 4 because they maintained or even slightly increased in weight during that time and had retained their CD4 and lymphocyte levels, albeit in very low numbers. The food supplements [P.P 80 + 2Leid + P.I. and tri-therapy] caused a dramatic gain in weight. More importantly, there was a spectacular increase in the number of their total lymphocytes. All were in a satisfactory state of health after 12 months of food supplements intake.

P.P.80, 2Leid and tri-therapy

Patients 5 to 8 received only P.P.80 + 2Leid, in addition to the chemicals. They were in a very poor state of health before starting food supplementation: severe drops in CD4 counts, except in patient 8, low weight and low lymphocyte count. The tri-therapy had proven ineffective. After three months of food supplement intake [P.P.80 + 2Leid + tri-therapy], lymphocyte counts increased dramatically and 3 out of 4 patients had a significant gain in weight. Patient 6 also gained weight after 12 months of alternative therapy and all were in a satisfactory state of health at that moment (T12).

PP 80 and tri-therapy

Patients 9 to 12 received P.P.80 in addition to the tri-therapy. Patients 9 and 10 were clinically speaking in a “stable state”, with relatively high CD4 and lymphocyte counts at time T0. The weight of patient 9 was not measured before the start of the study, but patient 10 had a stable weight. By contrast, patients 11 and 12 had low CD4 counts despite tri-therapy and had lost weight. The tri-therapy had proven inefficient. Three months after they started to take the P.P.80 food supplement, their weight and their lymphocyte counts had increased. After twelve months of treatment with the food supplement, their health was good.

PP20, Para Immuno and tri-therapy

This regimen was given to patient 13, a 15-years old girl weighing 24 kg at the time of her admission in the orphans’ home, under chemo-therapy but with diarrhea, fever and pneumopathy and having lost ¾ of her CD4's during chemical treatment, recovered when P.P.20 and P.I. was given during three months. The use of P.P.20 instead of P.P.80, a 4-fold lower dose in active principles, resulted in a similar weight gain and lymphocyte count recovery as with the previous 12 patients, indicating that this lower dosage was just as efficacious, at least in a teenager.

Patient 14, under tri-therapy and receiving only 2Leid as food supplement had a moderate CD4 cell count but was losing weight before joining the study. Three months later, she had not only recovered but gained weight and her lymphocyte count had doubled. These results are comparable to those observed in the other 13 patients.

Patients without tri-therapy

A larger number of patients (Table 2: Nb 15 to 60) received no tri-therapy. The clinician defined their health status at time zero by qualitative criteria (conserved, good, bad etc.) and took note of opportunist infections. The loss of weight in these AIDS patients from the moment of their admission in the orphans’ home (T-1) to time zero (T0), i.e. a year later when food supplementation started, is an objective sign of their evolution, as is their viral load and the level of their CD4’. Some of them, especially young children, gained weight and increased the number of CD4 while others saw a decline in their CD4 between T-1 and T0, but only two of them (Nbs 29 and 41) had CD4 levels below the 100 mark at time T0.

Table 2 shows that, irrespective of the severity of their illness and the worsening of their physical condition during the year that preceded supplement treatment, all recovered and gained weight in addition to increasing their total lymphocyte count. All were in satisfactory or good health at the end of the twelve-month course of food-treatment. If the effects of this treatment are visible after three months in most of the treated AIDS people, some however needed more than three months of food supplement intake before showing clear evidence of recovering health (Nbs 21, 27, 56) even if an increase in numbers of total lymphocytes took already place at time T3.

Discussion

During the whole year of treatment with natural products, we deplored no collateral secondary effects except two patients on PP80, who signalled a nose blooding that disappeared after the end of the treatment. This evidence of innocuity corroborates the results obtained in animal studies (Federlin et al., 2014).

All applied protocols proved efficacious. The uleine boosts the synthesis of nitric oxide, the ribonucleotides stimulate the multiplication of lymphocytes and the Para Immuno (propolis, Royal jelly and pollen) stimulates the immune system. A combination of all three works best in as much that every facet of the global treatment was exploited. However, the single application of uleine to non-treated patients, be it at its highest or lowest concentration, yielded remarkable results by itself. Patients 26, 27 and 28, who were given PP80, showed a substantial improvement of their condition, at a par with that observed when complete regimens were given. This observation is valid also for patients 47 to 51, who received PP20: their condition improved at the same rate as patients handled with the two additional food supplements. The chemically unattended patients were generally in a better condition (i.e. said “conserved”) than those who were under treatment. In this group, patients 9, 10, 11 and 12 gained no weight during chemical treatment or else lost weight. Yet, PP80 given alone to them in addition to tri-therapy improved considerably their health. An explanation for this remarkable effect may be found in the fact that uleine also interferes with the inflammatory response (Nardin et al., 2008) and regulates the immune system (Nardin et al., 2010). The substance possesses thus properties shared by the two other regimen proposed. One must note here that a reduction in the number of pills taken, and in the frequency of their administration, must be favoured in all cases not only for reasons of cost and burden but because it plays a considerable positive role on the psychology of the patients.

The progress registered initially on the clinical level by nearly all patients receiving food supplements was confirmed by a significant increase of total lymphocytes numbers and weight increase from the 3th month on. Patients under tri-therapy progressed most obviously at the level of secondary effects and opportunistic infections. In 2006, at the end of the supplement treatment, we registered no case of diarrhoea, no case of hyperthermia, no case of dermatose or other opportunistic illnesses. We had only three deaths by pneumocytosis, meningitis and bacterial pneumopathy but these were very advanced cases at the beginning of the treatment.

The patient under tri-therapy were given food supplements when they showed no improvement and/or developed opportunistic diseases that did not exist before the treatment with the anti-retrovirals. A tri-therapy based on stavudine, lamivudine and nevirapine is a heavy treatment that often causes secondary effects in the patient and can be a factor of health degradation in many treated subjects. Our results indicate that tri-therapy worsens the health of some AIDS patients instead of improving it, while taking food supplements not only does not cause the same negative effects but can help the patients get over those produced by conventional therapy and even cause partial recovery of AIDS patients not receiving it.

Acknowledgment

Doctor Christian Bouillon and Chloe Ndayikunda provided us with the files of the patients.

References

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Received: May 24, 2014; Accepted: November 04, 2014

*Corresponding author. E-mail: anda.mars@wanadoo.fr (R. Maes).

Conflicts of interest

All authors have none to declare

Authors' contributions

DM contributed in the fabrication of the food supplements, delivery and follow up; and RM analysed the raw data, exploited them and wrote the manuscript. Both authors have read and approved the paper for submission.

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